Audio Journal of Oncology Podcast

Icro Meattini MD; 2026 EBCC: Safe to Avoid Endocrine Therapy in Older Women with Low Risk Breast Cancers: EUROPA Study Interim Findings

Audio Medica News — Thu, 16 Apr 2026 11:28:53 +0000

Safe to Avoid Endocrine Therapy in Older Women with Low Risk Breast Cancers: EUROPA Study Interim Findings

An interview with:

Icro Meattini MD, Associate Professor of Radiotherapy, University of Florence, Clinical Oncologist, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Italy

BARCELONA, Spain—More evidence has emerged showing that older women with breast cancers that are not life threatening can safely receive only radiotherapy after breast conserving therapy, without adding hormone treatments. At the 2026 European Breast Cancer Conference emerging findings from the EUROPA study of women over 70 with “luminal-like” early breast cancer were discussed by Icro Meattini MD, Associate Professor of Radiotherapy at the University of Florence, and Clinical Oncologist at Azienda Ospedaliero-Universitaria Careggi, University of Florence, Italy. He talked with Peter Goodwin about the findings and clinical implications:

AUDIO JOURNAL OF ONCOLOGY: Iccro Mettini MD

IN: [GOODWIN]”Peter Goodwin here in Barcelona…..

OUT: ….. of Oncology, I’m Peter Goodwin

2026 European Breast Cancer Conference:

“EUROPA Study: Endocrine or Radiation Therapy for Elderly Patient with Small Early Breast Cancers, Luminal A-like”

(Follow up from SABCS interim findings report (2024))

DETAILS:

At SABCS 2024, Dr. Icro Meattini presented a preplanned interim analysis of the EUROPA trial, a randomized phase III study comparing exclusive endocrine therapy (ET) vs. radiation therapy (RT) in women aged 70+ with luminal-like early breast cancer. The study aimed to evaluate quality of life (HRQOL) and ipsilateral breast tumor recurrence (IBTR) to guide treatment decisions in this patient population.

Key Findings:

RT preserved HRQOL scores better than ET at 24 months (mean change: -3.4 RT vs. -9.79 ET, p=0.045).

Treatment-related adverse events (AEs) were lower in the RT arm (67%) compared to the ET arm (85.4%).

No significant differences in IBTR rates at this interim analysis, but longer follow-up is needed for definitive conclusions.

RT showed better functional outcomes compared to ET across multiple QLQ-C30 domains

Clinical Implications:

These results suggest that both RT and ET may be viable single-modality treatment options in this population, with HRQOL and toxicity profiles playing a key role in treatment selection. The study underscores the importance of multidisciplinary, patient-centered approaches in older women with early-stage breast cancer.

2024 EUROPA Findings:

Looking back at SABCS 2024, the EUROPA trial continues to provide valuable insights into optimizing treatment decisions for older breast cancer patients.

SABCS PAPER (Lancet Oncology):

00661-2/abstract

Single-modality endocrine therapy versus radiotherapy after breast-conserving surgery in women aged 70 years and older with luminal A-like early breast cancer (EUROPA): a preplanned interim analysis of a phase 3, non-inferiority, randomised trial

Icro Meattini, MDa,b icro.meattini@unifi.it ∙ Maria Carmen De Santis, MDc ∙ Luca Visani, MDb ∙ Prof Marta Scorsetti, MDd ∙ Alessandra Fozza, MDe ∙ Bruno Meduri, MDf ∙ et al. Show more

Background

Optimal therapy following breast-conserving surgery in older adults with low-risk, early-stage breast cancer remains uncertain. The EUROPA trial aims to compare the effects of radiotherapy and endocrine therapy as single-modality treatments on health-related quality of life (HRQOL) and ipsilateral breast tumour recurrence (IBTR) outcomes in this population.

Methods

This non-inferiority, phase 3, randomised study was conducted at 18 academic hospitals across Italy (17 centres) and Slovenia (one centre). Eligible patients were women aged 70 years or older with histologically confirmed, stage I, luminal A-like breast cancer, who had undergone breast-conserving surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive single-modality endocrine therapy or radiotherapy. Endocrine therapy consisted of daily oral aromatase inhibitors or tamoxifen, for a total planned duration of 5–10 years as per clinical discretion, while radiotherapy was administered as either whole breast or partial breast irradiation, delivered in 5–15 fractions. Randomisation was stratified by health status according to the Geriatric 8 (G8) screening tool and by age, with allocation concealed and no blinding. The co-primary endpoints were the change in HRQOL, assessed by the global health status (GHS) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core module at 24 months, and 5-year IBTR rates (not reported here). This preplanned interim analysis was performed once at least 152 patients completed the 24-month GHS HRQOL assessment. The safety population comprised patients who received the study intervention at least once after randomisation. The study is registered with ClinicalTrials.gov, NCT04134598, and is ongoing and actively recruiting.

Findings

Between March 4, 2021, and June 14, 2024, 731 women were randomly assigned to receive radiotherapy (n=365) or endocrine therapy (n=366). This analysis included 104 patients in the radiotherapy group and 103 in the endocrine therapy group, with a median follow-up of 23·9 months (IQR 22·9–24·2). Patients were predominantly White (204 [99%] of 207) and the median age was 75·0 years (IQR 73·0–80·0) in the radiotherapy group and 74·0 years (72·0–80·0) in the endocrine therapy group. 86 patients in the radiotherapy group and 75 in the endocrine therapy group completed the 24-month HRQOL assessment. The mean baseline GHS score was 71·9 (SD 19·1) in the radiotherapy group and 75·5 (19·3) in the endocrine therapy group. At 24 months, the age-adjusted, G8 score-adjusted mean change from baseline in GHS was –3·40 (95% CI –7·82 to 1·03; p=0·13) in the radiotherapy group and –9·79 (–14·45 to –5·13; p<0·0001) in the endocrine therapy group, with an adjusted mean difference of 6·39 (0·14 to 12·65; p=0·045) favouring radiotherapy. Treatment-related adverse events were less frequent in the radiotherapy group (65 [67%] of 97 patients) compared with the endocrine therapy group (76 [85%] of 89). The most common grade 3–4 adverse events were arthralgia (six [7%] of 89 in the endocrine therapy group vs 0 of 97 in the radiotherapy group), pelvic organ prolapse (three [3%] vs 0), fatigue, hot flashes, myalgia, bone pain, and fractures (two [2%] vs 0 for each). Serious adverse events were reported in 15 (15%) patients in the radiotherapy group and 13 (15%) in the endocrine therapy group. There were no treatment-related deaths in either group.

Interpretation

Endocrine therapy was associated with a greater reduction in HRQOL, as measured by GHS, compared with radiotherapy at 24 months. While these interim results suggest radiotherapy might better preserve HRQOL in older women with low-risk early breast cancer, further data on disease control outcomes and final patient accrual are needed to draw definitive conclusions.

EBCC 2026 Icro Meattini MD Audio Journal of Oncology TEXT

Amparo Garcia-Tejedor MD, PhD; 2026 EBCC: Axillary Radiotherapy Seems As Effective as Axillary Lymphadenectomy in Sentinel Node Positive Early Breast Cancer, with Less Risk of Lymphedema

Audio Medica News — Mon, 13 Apr 2026 17:07:42 +0000

Axillary Radiotherapy Seems As Effective as Axillary Lymphadenectomy in Sentinel Node Positive Early Breast Cancer, with Less Risk of Lymphedema

An interview with:

Amparo Garcia-Tejedor MD, PhD, Professor of Gynecology, University of Barcelona, Bellvitge University Hospital, Instituto de Investigación Biomédica de Bellvitge, Barcelona, Spain.

BARCELONA, Spain—Early results from the ADARNAT study have found that using axillary radiotherapy after neoadjuvant therapy and surgery for women with sentinel node positive early breast cancer was as effective removing lymph nodes while bringing a lower risk of lymphedema. These preliminary finding were reported at the 2026 European Breast Cancer Conference by Amparo Garcia-Tejedor MD, PhD, Professor of Gynecology at the University of Barcelona’s Bellvitge Hospital, in Barcelona, Spain. Afterwards she gave more details to our reporter, Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Amparo Garcia-Tejedor MD, PhD

IN: [GOODWIN]”Peter Goodwin here in…..

OUT: …..of Oncology, I’m Peter Goodwin 6:36secs

EBCC Abstract 7:

Axillary radiotherapy as an alternative to axillary dissection for node-positive breast cancer after neoadjuvant therapy: two-year survival results from the ADARNAT pilot phase

Garcia-Tejedor1, M. Laplana2, S. Salinas3, A. Luzardo3, M. Campos1, C. Ortega1,
Martinez4, M.J. Pla1, A. Guma5, J.G. Reyes-Junca6, S. Pernas7, C. Falo7, J. Azcarate8, J. Ponce1, Spanish ADARNAT Group

1Hospital Universitari de Bellvitge, Gynecology, Hospitalet de Llobregat, Spain

2Hospital Clínic de Barcelona, Oncological Radiotherapy, Barcelona, Spain

3Hospital Universitari de Bellvitge, Rehabilitation, Hospitalet de Llobregat, Spain

4Institut Català d’Oncología, Oncological Radiotherapy, Hospitalet de Llobregat, Spain

5Hospital Universitari de Bellvitge, Radiology, Hospitalet de Llobregat, Spain

6Hospital Universitari de Bellvitge, Nuclear Medicine, Hospitalet de Llobregat, Spain

7Institut Català d’Oncologia, Medical Oncology, Hospitalet de Llobregat, Spain

8Hospital Universitari de Bellvitge, Pathology, Hospitalet de Llobregat, Spain

Background:

After neoadjuvant therapy (NAT), the optimal management of sentinel lymph node (SLN)-positive axilla remains controversial. Current guidelines still recommend axillary lymphadenectomy (ALND), although evidence increasingly supports less invasive approaches. The ADARNAT trial investigates whether axillary radiotherapy (ART) without lymphadenectomy can safely replace ALND in patients with limited nodal disease after NAT.

Methods:

ADARNAT is an open-label, randomized, phase III multicenter trial across 23 Spanish hospitals. Eligible patients had cT1–T4b, cN0–cN1 breast cancer treated with NAT (chemotherapy or endocrine therapy) and 1–2 positive SLNs (micro- or macrometastases) at surgery. Participants were randomized to ART (experimental arm) or ALND (control arm). Both arms received regional radiotherapy to level III axilla and supraclavicular and/or internal mammary nodes, plus breast/chest wall irradiation when indicated. This report summarizes pilot phase outcomes assessing feasibility and short-term safety.

Results:

From June 2021 to April 2023, 272 patients were enrolled; 102 completed per protocol (46 ART, 56 ALND) with a median follow-up of 2 years. Baseline and pathological characteristics were balanced between arms (Table). No axillary recurrences occurred in the ART arm and one in the ALND arm (1.8%, p=0.3). Distant metastases occurred in 4.4% vs 5.5% (p=0.8), and two deaths were reported in the ALND group (4.3%, p=0.2). Lymphedema was more frequent after ALND (26.7%) than ART (18.9%) without statistical significance (p=0.4). Two-year disease-free and overall survival rates were comparable, supporting the feasibility and short-term oncologic safety of ART.

Conclusions:

The ADARNAT pilot phase suggests that axillary radiotherapy may achieve similar short-term oncologic outcomes to axillary lymphadenectomy in SLN-positive breast cancer after NAT, with comparable toxicity and a trend toward reduced morbidity. These preliminary results support the continuation of the phase III trial to confirm long-term non- inferiority and potential quality-of-life benefits of omitting axillary surgery.

2026 EBCC PRESS RELEASE:

Radiotherapy rather than surgery may help reduce risk of lymphoedema in patients with breast cancer: results from pilot study

Barcelona, Spain: Patients with breast cancer may be able to avoid lymphoedema, which can occur after surgery to remove lymph nodes in the armpit (the axilla), by having radiotherapy instead.

New findings, presented at the 15th European Breast Cancer Conference (EBCC15) in Barcelona today (Thursday), suggest that axillary radiotherapy may be as effective at killing any remaining cancer cells, while being less likely to trigger lymphoedema – an often painful swelling of the arm and armpit.

These results come from the pilot phase of a phase III randomised international clinical trial [1, 2] that is investigating whether axillary radiotherapy (ART) has a lower risk of lymphoedema than axillary lymph node dissection (ALND) in patients with breast cancer who have received neoadjuvant systemic therapy, such as chemotherapy or hormone therapy, before surgery, and in whom cancer has spread to only one or two lymph nodes. The trial will also be looking at overall survival and disease-free survival.

The researchers stress that these are preliminary results from two years of follow-up in the pilot study, and that clinicians should wait for the results from the phase III part of the trial, which is ongoing, before considering changing clinical practice.

Professor Amparo Garcia-Tejedor, from the Functional Breast Unit at Bellvitge University Hospital, Spain, and the Institut Català d’Oncologia, is leading the trial. She told the conference that studies had already shown that ART was a good alternative to ALND in patients for whom the first line of treatment was surgery.

“In situations where patients have received chemotherapy or hormone therapy before surgery, it is expected that results could be similar,” she said. “However, robust prospective data are not yet fully established or published.

“Many patients treated with neoadjuvant therapy experience a significant reduction in axillary disease burden and ultimately present with only one or two lymph nodes that are positive for cancer metastases, which often correspond to the sentinel lymph node, while the remaining axillary nodes are negative. This observation strongly suggested that further axillary surgery might be unnecessary in a substantial proportion of patients and that a strategy of de-escalation should be explored.”

From June 2021 to April 2023, the ADARNAT trial (ALND vs ART in Positive Sentinel Node After Neoadjuvant Therapy in Breast Cancer) recruited 272 patients with breast cancer, which might have spread (metastasised) to one or more lymph nodes. The patients had received neoadjuvant therapy and, at the time of surgery, had metastatic cancer in one or two sentinel lymph nodes (the lymph nodes where cancer typically metastasises first). The patients were randomised to receive either ART or ALND; patients in both arms of the trial also received radiotherapy to areas of the breast and chest. Results were available for 46 patients in the ART group and 56 patients in the ALND group, with a median follow-up period of two years.

No cancer recurred in the axillary area in the ART group and one recurred in the ALND group (1.8%). Cancer metastasised to other parts of the body in 4.4% versus 5.5% of the patients, respectively, and there were two deaths in the ALND group (4.3%). Lymphoedema occurred more frequently after ALND (26.7%) than ART (18.9%), although this was not statistically significant. Disease-free and overall survival rates were similar after two years of follow-up.

Prof. Garcia-Tejedor said: “These results indicate that ART instead of ALND is feasible and has good cancer outcomes at two years.

“While some specialists have already begun to substitute axillary lymph node dissection with axillary radiotherapy without waiting for definitive results, the only way to determine with certainty whether this strategy is truly safe and effective is through participation in a well-designed clinical trial such as the one we are now conducting. This is particularly important given that the study population includes patients with residual axillary disease and, therefore, a potentially worse prognosis.

“In this context, treatment decisions should not be made without robust evidence. Our trial is designed to provide the necessary data to definitively answer this question and to ensure that any future change in standard practice is safe in terms of cancer outcomes and is also beneficial for patients.”

Dr Maria Laplana-Torres is a radiation oncologist at the Hospital Clínic de Barcelona, Spain. She presented results from the pilot phase of the trial that showed that although ART was associated with more damage to the skin from radiation, this tended to be transient and easily treatable.

Acute skin damage (grade 2 or above) occurred in 27.8% of ART patients compared with 13.3% after ALND. It consisted mainly of skin redness, pigment changes or skin peeling in some cases. There were no significant differences in later skin damage between the two groups.

She said: “Some patients experienced mild, temporary difficulty raising the arm above the shoulder or lifting it to the side. These limitations were usually short-lived and did not affect everyday activities.

“We found that treating the axilla with radiotherapy instead of extensive surgery can avoid a more aggressive operation without compromising treatment safety in patients with sentinel lymph node involvement. One and two years after treatment, there were no meaningful differences in arm mobility or quality of life between the two groups, although there was a more favourable trend in the ART patients. These results show that axillary radiotherapy may be a safe and less invasive option for some women treated with chemotherapy or hormone therapy before surgery.

“This kind of research is essential to continue improving patient outcomes and to define safer, equally effective therapeutic approaches.”

So far, more than 500 patients have joined the main, phase III clinical trial. The researchers estimate that approximately three more years will be required to complete patient recruitment. This will then be followed by the planned five years of follow-up to fully assess cancer outcomes.

Prof. Garcia-Tejedor concluded: “If the study confirms the safety and effectiveness of axillary treatment de-escalation, the implications for both patients and clinicians could be substantial. For patients, the main potential benefit would be an improvement in quality of life, particularly through a reduction in lymphoedema and other functional complications associated with axillary surgery. For clinicians, these findings would support a paradigm shift in axillary management, reinforcing the move away from routine extensive surgery toward more personalised and less morbid treatment strategies, while maintaining good cancer outcomes.

The Chair of EBCC15, Professor Isabel Rubio, Head of Breast Surgical Oncology at the Clínica Universidad de Navarra in Madrid, Spain, was not involved in this research. She commented: “These findings from the pilot phase of the phase III ADARNAT clinical trial are encouraging. They provide a sound basis for the clinical trial to proceed. Once the trial reports its final results in a few years’ time, we will know whether radiotherapy rather than surgery is safe for patients who have received neoadjuvant treatments.

“While this trial suggests a promising trend towards lower lymphoedema rates with radiation therapy, the next important step is to determine in which patients it may be safe to omit radiation altogether in order to further individualise breast cancer care. Surgical treatment for breast cancer has already moved towards de-escalation, with many patients now able to avoid full axillary lymph node dissection and its associated side effects. However, despite these advances, a significant number of patients still face an increased risk of lymphoedema after radiation therapy. Future research should focus on identifying the subgroup of patients who may not benefit from either axillary dissection or radiation therapy, thereby helping to minimise treatment-related complications while maintaining excellent cancer outcomes.”

260413 Amparo Garcia-Tejedor, 2026 EBCC A J Oncology TEXT

Eline Verreck BSc; 2026 EBCC: Radiation Boost May No Longer Be Justified After Standard Therapy for Early Breast Cancer

Audio Medica News — Mon, 06 Apr 2026 16:19:04 +0000

Radiation Boost May No Longer Be Justified After Standard Therapy for Early Breast Cancer

An interview with:

Eline Verreck BSc, Erasmus University Medical Centre, Surgical Oncology Department, Rotterdam, The Netherlands

BARCELONA, Spain—Any benefit from an additional tumor-bed radiotherapy “boost” after completing standard therapy for early breast cancer seems no longer to be justified in this age of increasingly effective systemic treatments now being incorporated into standard breast-conserving therapy. A new study conducted in the Netherlands, with 34,504 patients followed up for a median of 8.3 years, has found that the possible small reductions of long-term local recurrence rates from using a boost no longer justify the toxicities such a boost can bring.

Findings were reported at the 2026 meeting of the European Breast Cancer Conference by Eline Verreck BSc, who is a PhD candidate at Erasmus University Medical Centre’s Department of Surgical Oncology in Rotterdam. She talked about her results with the Audio Journal of Oncology’s correspondent, Peter Goodwin:

AUDIO J0URNAL OF ONCOLOGY: Eline Verreck BSc

IN: [GOODWIN]” Welcome to more news here from the …..

OUT: …….I’m Peter Goodwin for the Audio Journal of Oncology 7:00secs

EBCC 2026 ABSTRACT PPT-054

“The relevance of a boost in the current era of systemic therapy after breast-conserving surgery and radiotherapy”

Verreck1,, W.D. Heemsbergen2,, T. van Dalen3,, S. Windhorst4,, L. de Munck4,, F. van der Leij5,, L.J. Boersma6,, F.E. Froklage2,.

1Erasmus University Medical Centre, Surgical Oncology, Rotterdam, The Netherlands.

2Erasmus University Medical Centre, Department of Radiation Oncology, Rotterdam, The Netherlands.

3Erasmus University Medical Centre, Department of Surgical Oncology, Rotterdam, The Netherlands.

4Netherlands Comprehensive Cancer Organisation, Department of Research and Development, Utrecht, The Netherlands.

5University Medical Centre Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands.

6Grow Research Institute for Oncology and Reproduction- Maastricht University Medical Centre+, Department of Radiation Oncology Maastro, Maastricht, The Netherlands.

Background:

Breast-conserving surgery (BCS) is commonly followed by whole breast radiotherapy (WBRT), which may include a boost to the tumour bed. The former boost trial (Bartelink, 2015) showed a 50% reduction in local recurrence (LR) risk. However, systemic therapy has evolved substantially since then, resulting in an absolute LR risk of <5% at 10 years. In the current era, a boost may therefore represent overtreatment. Moreover, it is associated with increased fibrosis risk and poorer cosmetic outcomes. The Assisi Think Tank Meeting 2024 suggested omission of a boost in patients whose 10-year LR risk without a boost is <6%. Therefore, this study aims to identify patients with a 10-year LR risk of <6% after WBRT without a boost, and patients with a 10-year LR risk of <3% after WBRT with a boost.

Methods:

This study included all Dutch breast cancer (BC) patients treated with BCS and adjuvant WBRT between 2012-2016. Data were obtained from the Netherlands Cancer Registry, and information on LR was collected through linkage with PALGA, the nationwide pathology database. Using this methodology, LR data completeness is estimated to be approximately 80% (van Maaren, 2025). The LR risk was described for patients treated without and with boost, and for subgroups defined by known risk factors within these two categories.

Results:

A total of 34,504 patients with a median follow-up of 8.3 years were included. Four percent were ≤40 years old, 23% had grade 3 tumours, 11% had triple-negative BC, and 6% had focally positive margins, with 90%, 82%, 75%, and 87% of each group receiving a boost, respectively. (Neo)adjuvant systemic therapy was administered to 64% of patients (39% chemotherapy +/- targeted therapy, 52% endocrine therapy). LR occurred in 343 patients (1.0%), of whom 174 (51%) had solitary LR, and 169 (49%) also developed regional recurrence and/or distant metastases. Among 15,953 patients who did not receive a boost, 0.9% developed LR, and among 17,321 patients who received a boost, 1.1% developed LR. In all subgroups, the 8.3-year LR rate was below 6% (without boost) and 3% (with boost) (Table 1), even after adjusting for 80% completeness.

Conclusions:

The LR rate in BC patients treated with BCS and WBRT was 1.0% at a median follow-up of 8.3 years. In subgroups of patients treated without or with boost, LR rates did not exceed 6% and 3%. These findings hypothesize that, when patients are categorized by univariable risk factors, a boost may no longer be clinically relevant in the modern systemic therapy era.

https://www.ejcancer.com/article/S0959-8049(26)00084-5/abstract

Eline Verreck 2026 EBCC Audio Journal of Oncology Text

Fleur Mauritz MD; EBCC 2026: RAPCHEM Study Shows Risk-Based Radiotherapy De-Escalation is Safe After Primary Systemic Therapy for Early Breast Cancer

Audio Medica News — Fri, 03 Apr 2026 11:44:26 +0000

RAPCHEM Study Shows Risk-Based Radiotherapy De-Escalation is Safe After Primary Systemic Therapy for Early Breast Cancer

An interview with:

Fleur Mauritz MD, Resident in Radiation Oncology, MAASTRO Institute of Radiation Oncology and Research, Maastricht, Netherlands

BACELONA, Spain—Radiation therapy after primary systemic therapy for early breast cancer can be safely de-escalated according to risk in the light of 10-year follow-up findings from the RAPCHEM study reported at the 2026 European Breast Cancer Conference.

First author Fleur Mauritz MD, who is a resident in radiation oncology at the MAASTRO Institute of Radiation Oncology and Research in Maastricht, Netherlands, gave the Audio Journal of Oncology’s Peter Goodwin the latest:

AUDIO JOURNAL OF ONCOLOGY; Fleur Mauritz MD

IN: [GOODWIN]”….Welcome to the …..

OUT: ….for the Audio Journal of Oncology, Goodbye.” 6:08secs

EBCC 2026 Abstract no: 1,

‘Radiotherapy Long term results of Radiation therapy de-escalation in cT1-2N1 breast cancer After Primary CHEMotherapy (RAPCHEM: BOOG 2010-03): 10-year follow-up results of a Dutch, prospective, registry study’

Authors:

Mauritz1,, L. de Munck2,, J. Simons3,, J. Verloop2,, T. van Dalen4,, P. Elkhuizen5,, A. Scholten5,, R. Houben1,, A.E. van Leeuwen6,, S. Linn7,, R. Pijnappel8,, P. Poortmans9,10, L. Strobbe11,, J. Wesseling12,, A. Voogd2,13, L. Boersma1,.

1Maastricht University Medical Centre+, Dept. of Radiation Oncology Maastro- GROW Research Institute for Oncology and Developmental Biology, Maastricht, The Netherlands.

2Netherlands Comprehensive Cancer Organisation, Dept. of Research and Development, Utrecht, The Netherlands.

3Erasmus MC, Dept. of Radiation Oncology, Rotterdam, The Netherlands.

4Erasmus MC, Dept. of Surgery, Rotterdam, The Netherlands.

5Antoni van Leeuwenhoek Hospital, Dept. of Radiation Oncology, Amsterdam, The Netherlands.

6f Dutch Breast Cancer Research Group, BOOG Study Center, Amsterdam, The Netherlands.

7Antoni van Leeuwenhoek Hospital, Dept. of Medical Oncology, Amsterdam, The Netherlands.

8University Medical Centre Utrecht, Dept. of Radiology, Utrecht, The Netherlands.

9Iridium Netwerk, Dept. of Radiation Oncology, Wilrijk-Antwerp, Belgium.

10University of Antwerp, Faculty of Medicine and Health Sciences, Wilrijk-Antwerp, Belgium.

11Canisius Wilhelmina Hospital Nijmegen, Dept. of Surgery, Nijmegen, The Netherlands.

12Antoni van Leeuwenhoek Hospital, Dept. of Pathology, Amsterdam, The Netherlands.

13Maastricht University Medical Centre+, Dept. Epidemiology- GROW Research Institute for Oncology and Developmental Biology, Maastricht, The Netherlands.

BACKGROUND

The five-year results of the RAPCHEM study (De Wild et al, 2022) and the recently published NSABP-B51 trial (Mamounas et al, 2025) suggest that locoregional radiation therapy (RT) can be tailored to the ypN-status in cT1-2N+ breast cancer (BC) patients treated with primary systemic treatment (PST). However, long-term results are lacking. Here we present the 10-year results of the RAPCHEM study, a prospective registry study, evaluating the long-term safety of tailoring locoregional RT to the nodal response after PST, for locoregional recurrence rate (LRR), recurrence free interval (RFI) and overall survival (OS).

MATERIAL AND METHODS

From January 2011 to January 2015, cT1-2N+M0 (<4 suspicious nodes at imaging) BC patients were prospectively included. Patients were treated with PST followed by lumpectomy or mastectomy in combination with a sentinel lymph node biopsy (SNLB) and/or removal of marked axillary lymph nodes (MARI), or an axillary lymph node dissection (ALND). cN+ status was histologically confirmed. Three risk groups were defined based on ypN-status, with corresponding RT strategy. Low-risk group (ypN0): whole breast RT (WBRT) after lumpectomy, no RT after mastectomy. Intermediate-risk group (ypN1): WBRT or chest wall RT, and in case of no ALND, RT of axillary levels 1-2. High-risk group (ypN2+): WBRT or chest wall RT, RT of the non-resected part of the axilla (levels 3-4 after ALND, and levels 1-4 if no ALND) with/without internal mammary nodes RT. The endpoints of the current analysis were 10-year LRR, RFI and OS. RFI was defined as time between primary diagnosis until first event (either local, regional, or distant recurrence, or death from BC). Kaplan-Meier survival analysis was used, and log-rank test to compare differences between groups.

RESULTS

Of the 848 included patients, ten were lost to follow-up. Twenty-four patients had a LRR without synchronous distant metastases. The 10-year LRR was 2.7% for the total cohort, and 2.1%, 3.2% and 2.8% respectively, for the low-, intermediate- and high-risk group. The 10-year RFI was 79.2% and the 10-year OS was 83.0%, both with significant differences between risk groups (Table 1).

CONCLUSION

De-escalation of locoregional RT after PST appears to be safe in terms of LRR. Stratification in risk groups seems appropriate, even when omitting regional RT (and chest wall RT in case of mastectomy) in the low-risk group, and RT of levels 3-4 in the intermediate-risk group.

00080-8/abstract

PRESS RELEASE:

Breast cancer recurrence remains low, even after ten years, with radiotherapy tailored to patient’s individual risk

Barcelona, Spain: The chances of breast cancer recurring remain very low when patients are treated with radiotherapy that is tailored to their individual risk following chemotherapy and surgery. These are the findings of a ten-year study presented at the 15th European Breast Cancer Conference (EBCC15) in Barcelona today (Wednesday).

In the study, radiotherapy treatment was selected according to whether there were still signs of breast cancer cells in patients’ lymph nodes after chemotherapy and surgery. For women with no signs of cancer remaining in the lymph nodes, this approach meant minimal or even no radiotherapy. Scaling treatment down can in turn reduce side-effects for patients.

The research was presented by Dr Fleur Mauritz, a radiation oncologist in training at Maastro, Maastricht Radiation Oncology Institute, The Netherlands. She said: “For many patients with breast cancer, the first treatment is chemotherapy. This can shrink the tumour and kill off any cancer cells that are starting to spread into the body, before surgery.

“We know that radiotherapy reduces the risk of breast cancer recurrence, especially when patients have had surgery to remove a tumour, rather than the whole breast, and when there are signs of cancer in the lymph nodes. This study examined whether it’s possible to scale back radiotherapy in patients whose cancer shows a good response when chemotherapy is given prior to surgery.”

The study included 848 patients who were treated at 17 cancer centres in The Netherlands between 2011 and 2015. Each patient had a small breast tumour (measuring under five centimetres) with signs of cancer spread in only one, two or three lymph nodes.

Following chemotherapy and surgery, the patients were categorised into three different risk groups. Patients who no longer had signs of cancer in their lymph nodes were categorised as low risk and were given radiotherapy to the breast if their surgery removed the tumour, or no radiotherapy if they had their breast removed (mastectomy). Patients who had signs of cancer in only one to three lymph nodes were categorised as intermediate risk and treated with radiotherapy to the breast area without irradiating the nearby lymph nodes. Patients with signs of cancer in four or more lymph nodes, were categorised as high risk and treated with radiotherapy to the breast area and the lymph nodes in the surrounding area.

In the following ten years, only 24 out of all 838 patients who completed follow-up (2.9%) experienced a recurrence in the breast, chest wall or lymph nodes (without signs of cancer spread elsewhere in the body). In the low-risk group, seven out of 291 patients (2.4%) developed a recurrence; in the intermediate-risk group, 12 out of 370 patients (3.2%) developed a recurrence; and in the high-risk groups five out of 177 patients (2.8%) developed a recurrence. [1]

Dr Mauritz said: “The results of our study show that tailoring the extent of radiotherapy according to how well the chemotherapy has worked to treat cancer in the lymph nodes, leads to very low and reassuring recurrence rates in the breast and surrounding area. In a selected group of patients, we see very low recurrence rates even when we leave radiotherapy out completely.

“A major strength of our study is that it’s the first to demonstrate the benefits of tailoring radiotherapy for this group of patients over a ten-year period. It is important to note that most patients in the study underwent axillary lymph node dissection, a procedure that was common ten years ago but is used less often in current practice. This study did not compare patients treated with and without radiation therapy. For the final conclusion, we will have to wait for the results of a randomised trial from the USA, which are expected in three years.” [2]

Dr Mauritz and her colleagues plan to study more about the risk factors for breast cancer recurrence, for example looking at tumour characteristics, and precisely where cancer recurs, to help refine radiotherapy in the future.

The Chair of EBCC15, Professor Isabel Rubio, Head of Breast Surgical Oncology at the Clínica Universidad de Navarra in Madrid, Spain, was not involved in this research. She said: “Reducing radiotherapy after chemotherapy appears safe in terms of the risk of recurrence. Choosing the amount of treatment based on the risk of recurrence also seems appropriate: radiotherapy may be omitted in low-risk patients after mastectomy, while in intermediate-risk patients, targeted radiotherapy remains advisable. Overall, this study reinforces that stratifying patients by risk, which supports more personalised treatment, helps to ensure the most appropriate approach while avoiding both overtreatment and undertreatment.”

Dr Mauritz is delivering the young investigator innovation award lecture at EBCC15.

Fleur Mauritz, Audio Journal of Oncology EBCC TEXT 2026 April 3rd, 2026

Jelle Wesseling MD PhD; 2026 EBCC: ‘Lord’ Trial Finds Active Surveillance for Estrogen-Receptor-Positive, HER2- Negative, Grade 1–2 DCIS Just As Effective as Standard Therapy

Audio Medica News — Thu, 02 Apr 2026 17:08:13 +0000

‘Lord’ Trial Finds Active Surveillance for Estrogen-Receptor-Positive, HER2-Negative, Grade 1–2 DCIS Just As Effective as Standard Therapy

An interview with:

Jelle Wesseling MD PhD, Pathologist, Medical Director, Early Cancers Detection Centre, Netherlands Cancer Institute, Division of Molecular Pathology, Amsterdam, The Netherlands.

BARCELONA, Spain: Because low-risk ductal carcinoma in situ (DCIS) is often unlikely to progress to breast cancer, de-escalating therapy was on the agenda of the Lord trial of active surveillance, that was reported at the 2026 European Breast Cancer Conference. The findings were reassuring: So much so that randomization was stopped early. The lead study author, pathologist Jelle Wesseling MD PhD who is Medical Director of the Early Cancers Detection Centre at the Netherlands Cancer Institute in Amsterdam, gave the details to the Audio Journal of Oncology’s Peter Goodwin.

AUDIO JOURNAL OF ONCOLGY: Jelle Wesseling MD PhD

IN: [GOODWIN]” I am at the European Breast ….

OUT: ….of Oncology, I’m Peter Goodwin 10:34secs

EBCC 2025 Abstract no: 2LBA:

“De-escalating treatment for low-risk Ductal Carcinoma In Situ: early safety of active surveillance without endocrine therapy in the prespecified interim analysis of the LORD-trial* (BOOG 2014-04)”

Authors:

Wesseling1,2,3,4, M. Nieberg1, S. Aleikhaneshir1, L. Elshof1, R. Schmitz1, C. Sondermeijer5, S. Balduzzi5, K. Pengel5, J. Weiner1, M. Gerritsma6, E. Engelhardt6, E. Bleiker6, E. Verschuur7, I. Langerak8, R. Mann9, E. van Leeuwen-Stok10, E. Lips1, N. Bijker11, F. van Duijnhoven12

1The Netherlands Cancer Institute, Division of Molecular Pathology, Amsterdam, The Netherlands

2Leiden University Medical Center, Department of Pathology, Leiden, The Netherlands

3 The Netherlands Cancer Institute, Center of Early Cancer Detection, Amsterdam, The Netherlands

4The Netherlands Cancer Institute, Department of Pathology, Amsterdam, The Netherlands

5The Netherlands Cancer Institute, Biometrics Department, Amsterdam, The Netherlands

6The Netherlands Cancer Institute, Division of Psychosocial Research and Epidemiology, Amsterdam, The Netherlands

7Europa Donna & Dutch Breast Cancer Patient Association BVN, Patient Advocacy, Utrecht, The Netherlands

8Dutch Breast Cancer Patient Association BVN, Patient Advocacy, Utrecht, The Netherlands

9The Netherlands Cancer Institute, Department of Radiology, Amsterdam, The Netherlands

10BOOG Study Center, National Breast Cancer Trial Coordination, Utrecht, The Netherlands

11The Netherlands Cancer Institute, Depratment of Radiation Oncology, Amsterdam, The Netherlands

12The Netherlands Cancer Institute, Department of Surgical Oncology, Amsterdam, The Netherlands

Background

Active surveillance has been proposed as a de-escalation strategy for women with low-risk ductal carcinoma in situ (DCIS). The LORD-trial evaluates the safety of active surveillance compared with standard treatment in women with estrogen-receptor-positive, HER2- negative, grade 1–2 DCIS.

Methods

The LORD-trial is a multicentre study that followed a patient-preference design after initial randomization proved infeasible. The primary endpoint is ipsilateral invasive breast cancer (iiBC)-free rate at 10 years. A prespecified, non-binding interim futility analysis was planned after 60 iiBC events.

Results

DSMB prespecified interim analysis

1,423 women had been enrolled with a median follow-up of 23 months. The first n=73 were randomized between the two arms. After transforming to a patient preference design, n=1,025 patients opted for active surveillance and n=330 for standard treatment. No patients received endocrine therapy. On an intention-to-treat basis, iiBC occurred in 4/363 (1%) women allocated to standard treatment and 63/1,060 (6%) women undergoing active surveillance. Based on these findings, the Data Safety Monitoring Board (DSMB) advised cessation of registration and recruitment, while continuing follow-up of enrolled patients.

Cohort analysis

When iiBCs detected at primary surgery in the standard-treatment group were additionally considered, cumulative iiBC incidence was similar between strategies: 33/363 (9%) in the standard-treatment arm and 63/1060 (6%) in active surveillance. Cases with full pathology characteristics available – for 31 and 55, respectively – were compared between the two arms (Table 1).

Conclusions

The prespecified DSMB interim analysis resulted in a recommendation to stop inclusion for reasons of futility, leading to early closure of trial inclusion. Follow-up of included women was recommended and is ongoing to assess long-term outcomes and inform the safety of de-escalation strategies for DCIS.

Table 1. Comparison iiBCs with fully known pathology characteristics per arm in the cohort analysis

https://cm.eortc.org/cmPortal/Searchable/ebcc15/config/Normal#!abstractdetails/0000992920

https://clinicaltrials.gov/study/NCT02492607

Jelle Wesseling Audio Journal of Oncology TEXT

April 2nd, 2026

Elisa Agostinetto MD; 2026 EBCC: Circulating Tumor DNA Trumps Clinical Prognostic Markers After Neoadjuvant Therapy for Patients with Early Breast Cancer

Audio Medica News — Wed, 01 Apr 2026 22:49:43 +0000

Circulating Tumor DNA Trumps Clinical Prognostic Markers After Neoadjuvant Therapy for Patients with Early Breast Cancer

An interview with:

Elisa Agostinetto MD, Institut Jules Bordet, Brussels, Belgium

BARCELONA, Spain—Among patients being treated with neoadjuvant therapy for their early breast cancers, circulating tumor DNA performed better as an independent prognostic marker for predicting relapse and disease progression than clinical markers such as pathological complete remission. This was according to prospective study data from Belgium and Italy reported at the 2026 European Breast Cancer Conference by Elisa Agostinetto MD, a medical oncologist from the Institut Jules Bordet in Brussels. She discussed her findings with Audio Journal of Oncology reporter, Peter Goodwin:

AUDIO J0URNAL OF ONCOLOGY: Elisa Agostinetto MD

IN: [GOODWIN] “I’m here at the ……

OUT: ……of Oncology, I’m Peter Goodwin 10:04secs

EBCC 2026:

Abstract no: 12

Circulating tumor DNA at completion of neoadjuvant therapy is an independent prognostic marker: an individual patient-level pooled analysis of two prospective studies

Agostinetto1, V. Appierto2, P. Minicozzi3, C. Sotiriou1, F. Rothé1, E. Tamborini2, F. Lebrun4,
Belfiore2, D. t’Kint4, L. De Cecco5, L. Buisseret4, M.C. De Santis6, A. Gombos4, G. Bianchi7,
Aftimos4, P. Verderio3, D. Vincent4, G. Pruneri2, M. Ignatiadis4, S. Di Cosimo MD2

1Institut Jules Bordet- Université libre de Bruxelles ULB- Hôpital Universitaire de Bruxelles H.U.B, Breast Cancer Translational Research Laboratory, Brussels, Belgium

2Fondazione IRCCS Istituto Nazionale dei Tumori, Advanced Diagnostics, Milan, Italy

3Fondazione IRCCS Istituto Nazionale dei Tumori, Epidemiology and Data Science, Milan, Italy

4Institut Jules Bordet- Université libre de Bruxelles ULB- Hôpital Universitaire de Bruxelles H.U.B, Medical Oncology, Brussels, Belgium

5Fondazione IRCCS Istituto Nazionale dei Tumori, Experimental Oncology, Mian, Italy

6Fondazione IRCCS Istituto Nazionale dei Tumori, Radiation Oncology, Milan, Italy

7Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Oncology, Milan, Italy

Background:

Circulating tumor DNA (ctDNA) is a promising biomarker in early breast cancer. However, limited sample sizes in available clinical studies weaken neoadjuvant evidence.

Materials and methods: Data from two independent prospective observational studies, one at the Institut Jules Bordet (Brussels), and one at the Istituto Nazionale dei Tumori (Milan), were pooled at the individual patient level for joint analysis. In both studies, women with early breast cancer received neoadjuvant therapy and underwent primary tumor-informed ctDNA assays at predefined time points: baseline (before initiation of neoadjuvant therapy), end of neoadjuvant therapy before surgery (EoT), and during follow-up. Associations between ctDNA detection and clinico- pathological variables (age, tumor size [e.g. T ≤5 cm vs. >5 cm], hormone receptor status, HER2 status, and pathological complete response (pCR) were evaluated using χ2 or Wilcoxon tests, as appropriate. The effect of ctDNA on event-free survival (EFS) was analyzed by univariable and multivariable Cox proportional hazards models adjusted for relevant covariates. A two-sided p value< 0.05 was considered statistically significant.

Results:

A total of 81 patients were analyzed. Median age was 48 (range 27-75) years at diagnosis; most had T≤5 cm (72%), node positive (68%) and triple negative (60%) disease. Breast cancer events were 26 throughout a median follow-up of 7 years (IQR 5.3-8.8). ctDNA was detected in 31/54 (57.4%) plasma samples at baseline, and in 11/64 (17%) plasma samples at the EoT. The detection of ctDNA was significantly associated with hormone receptor-negative status both at baseline and at the EoT (p<0.05). No association with pCR was observed at any time point. Patients with baseline ctDNA detection showed a non significant trend toward worse EFS (HR 1.56, 95% CI 0.58-4.22). Notably, detection of ctDNA at the EoT predicted breast cancer events and remained independently associated with decreased EFS even after adjustment for all other clinicopathological variables including pCR (HR 3.58, 95% CI 1.33-9.60).

Conclusions:

This individual patient-level pooled analysis includes one of the largest numbers of events reported to date in the ctDNA literature. ctDNA predicted breast cancer relapse, particularly when detected at the end of treatment, supporting the use of ctDNA for post-neoadjuvant risk stratification and subsequent therapeutic strategies.

Kerstin Wimmer MD; 2026 EBCC: Polyurethane-Coated Implants Reduce Capsular Contracture Risk after Mastectomy with Radiotherapy for Breast Cancer

Audio Medica News — Tue, 31 Mar 2026 11:44:41 +0000

Polyurethane-Coated Implants Reduce Capsular Contracture Risk after Mastectomy with Radiotherapy for Breast Cancer

An interview with:

Kerstin Wimmer MD, Medical University of Vienna, Department of General Surgery, Vienna, Austria; Post-Doctoral Researcher, Karolinska Institute, Stockholm, Sweden

BARCELONA, Spain—Women who had mastectomy with immediate pre-pectoral breast reconstruction followed by radiotherapy had less risk of capsular contracture when polyurethane-coated breast implants were used rather than un-coated implants. This finding from the OPBC-09 PRExRT study was reported at the 2026 European Breast Cancer Conference by Kerstin Wimmer MD, from the Medical University of Vienna’s Department of General Surgery in Vienna, Austria, who is currently doing post-doctoral researcher at the Karolinska Institute in Stockholm, Sweden. After her presentation, she discussed the findings with Audio Journal of Oncology correspondent Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Kerstin Wimmer MD

IN: [GOODWIN]”Peter Goodwin here, reporting……

OUT: on Oncology, I’m Peter Goodwin

2026 EBCC: Barcelona

Abstract no: 2

The impact of polyurethane coated implants on the risk of capsular contracture after immediate prepectoral breast reconstruction in the setting of postmastectomy radiotherapy: the OPBC-09 PRExRT study

Wimmer1, R. Kiblawi2, F. Fitzal3, C. Kohl4, L. Stenman Skarsgård5, G. Franceschini6, D. Virzi7,
Molska8, J.M. Broyles9, A. Agrawal10, G. Montagna11, M. Rivas Ibarra12, M. Banys-Paluchowski13, M. Knauer14, E. Gonzales15, J. Letzkus Berrios16, G. Karadeniz Çakmak17, D. Vorburger18,
Ferrucci19, W.P. Weber20

OPBC study group

1Medical University of Vienna, Department of General Surgery, Vienna, Austria

2University Hospital Basel, Department of Gynaecology & Obstetrics, Basel, Austria

3Hanusch Hospital, Department of Breast Reconstruction, Vienna, Austria

4Kliniken Essen-Mitte, Interdisciplinary Breast Center, Essen, Germany

5Oslo University Hospital, Department of Plastic and Reconstructive Surgery, Oslo, Norway

6Fondazione Policlinico Universitario Agostino Gemelli IRCCS,

Department of Science and Health of Women- Children and Public Health, Rome, Italy

7Humanitas Istituto Clinico Catanese, Plastic Surgery Unit, Catania, Italy

8University Hospital Zielona Góra, Clinical Department of General and Oncological Surgery, Zielona Góra, Poland

9Dana Farber/Brigham Cancer Center, Division of Breast Surgery- Brigham and Women’s Hospital, Boston, USA

10Cambridge University Hospitals, Department of Breast Surgery, Cambridge, United Kingdom

11Memorial Sloan Kettering Cancer Center, Breast Service- Department of Surgery, New York, USA

12Arturo López Pérez Foundation, Department of Breast Surgery, Santiago, Chile

13University Hospital Schleswig-Holstein- Campus Lübeck, Department of Gynecology and Obstetrics, Lübeck, Germany

14Tumor and Breast Center Eastern Switzerland, Tumor and Breast Center, St.Gallen, Switzerland 15Sanatorio Modelo Quilmes, Department of Senology, Buenos Aires, Argentina

16San Borja Arriarán Clinical Hospital-Clínica MEDS, Breast Surgical Unit, Santiago, Chile 17Zonguldak Bülent Ecevit University Faculty of Medicine, Department of General Surgery, Zonguldak, Turkey

18University Hospital Zurich, Breast Cancer Center- Department of Gynecology, Zurich, Switzerland 19IRCCS, Veneto Institute of Oncology, Padova, Italy

20University Hospital Basel, Breast Clinic, Basel, Switzerland

Introduction

Patients with breast cancer undergoing mastectomy with implant-based breast reconstruction (IBBR), who are at high risk of locoregional recurrence, often require postmastectomy radiotherapy (PMRT), which increases the risk of capsular contracture (CC). The present study assessed the association between use of polyurethane coated (PUc) versus non-PUc implants and the need for surgical revision due to CC in the setting of PMRT.

Material and methods

This international multicenter retrospective real-world study included patients with breast cancer who underwent nipple- (NSM) or skin-sparing mastectomy (SSM) with prepectoral IBBR with or without PUc implants followed by PMRT. Primary endpoint was surgical revision due to CC and was analyzed using Cox regression models.

Results

1183 women treated between 2016 to 2022 at 19 sites in 13 countries (4 continents) were included. Of them, 773 (65.3%) underwent non-PUc IBBR and 410 (34.7%) PUc IBBR. Median age was 47 years (IQR 41-54) and median BMI was 24.4 kg/m2 (IQR 22-

27.6). Median follow-up was 30.8 months (IQR 18.4-45.4) in the non-PUc group and 37.4 months (IQR 30-46.2) in the PUc group (p<0.001).

Of 1183 patients, 863 (73%) had invasive ductal carcinoma and 654 (55.3%) hormone receptor–positive/HER2 negative disease, with a median Ki-67 of 25% (IQR 12-44%). Compared to PUc IBBR, use of non-PUc implants was associated with less frequent NSM (32.5% vs. 73.7%, p <0.001), more frequent use of synthetic mesh (20.3% vs. 1%, p <0.001) or acellular dermal matrix (20.3% vs. 1.2%, p <0.001), and with one-stage IBBR (76.6% vs. 92.2%, p <0.001).

Compared to PUc IBBR, use of non-PUc implants was associated with a higher rate of surgical revision due to CC (35.7% vs. 10.1%; hazard ratio [HR] 3.7, 95%CI 2.6-5.4, p <0.001). The rate of any CC was also significantly higher in the non-PUc compared to the PUc group (58.7% vs. 33.3%; HR 1.9, 95%CI 1.5-2.4, p <0.001).

The likelihood of major infection (OR 3.9, 95%CI 2.2-7.6, p<0.001), implant loss (OR 11, 95%CI 6.7-19.1, p<0.001), reoperation (OR 3.3, 95%CI 2.4-4.6, p <0.001) and implant exposure (OR 7.9, 95%CI 2.6-35,p=0.001) was also higher in the non-PUc group.

Conclusions

This study showed a strong association between use of non-PUc vs. PUc implants and higher likelihood of surgical revision due to CC, as well as higher risk of complications, in the setting of PMRT. These findings may inform implant selection and reconstructive planning for irradiated patients.

Kerstin Wimmer EBCC 2026 A. J. Oncology, March 31, 2026

Fatima Cardoso MD; 2026 EBCC: OASIS-4 Trial Finds Elinzanetant Cuts Vasomotor Symptoms (“Hot Flashes”) in Endocrine Therapy-Treated Patients with Breast Cancer

Audio Medica News — Mon, 30 Mar 2026 11:24:53 +0000

OASIS-4 Trial Finds Elinzanetant Cuts Vasomotor Symptoms (“Hot Flashes”) in Endocrine Therapy-Treated Patients with Breast Cancer

An interview with:

Fatima Cardoso MD, Medical Oncologist, Head of Clinical Research & International Collaboration in Breast Cancer, Centre Antoine Lacassagne, Nice, France

BARCELONA, Spain—Vasomotor symptoms, or “hot flashes”, were greatly reduced in the OASIS-4 phase three placebo-controlled trial among patients receiving endocrine therapy for their breast cancers who were randomized to treatment with the dual neurokinin receptor antagonist elinzanetant. This was in data reported to the 2026 European Breast Cancer Conference by Professor Fatima Cardoso, a medical oncologist who is Head of Clinical Research and International Collaboration in Breast Cancer at the Centre Antoine Lacassagne in Nice, France. After talking at the conference she met up with the Audio Journal of Oncology’s reporter, Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Fatima Cardoso MD

IN: [GOODWIN]”I am here now with Fatima ….

OUT: …..Oncology, I’m Peter Goodwin 10:30

EBCC 2026 ABSTRACT

Abstract no: 3

Efficacy of elinzanetant for the treatment of vasomotor symptoms in women with breast cancer: subgroup analysis of the OASIS-4 trial by type of endocrine therapy

Cardoso1, D. Brennan2, T. Simoncini3, L. Wahyudi4, K. Laapas5, C. Seitz6,7

1Champalimaud Clinical Center/Champalimaud Foundation and ABC Global Alliance, Breast Unit, Lisbon, Portugal

2UCD School of Medicine, Mater Misericordiae University Hospital, Dublin, Ireland

3University of Pisa, Department of Clinical and Experimental Medicine, Pisa, Italy

4Bayer CC AG, Medical & Evidence CGT- OPH & WHC CH, Basel, Switzerland

5Bayer Oy, Development- Pharmaceuticals, Espoo, Finland

6Bayer AG, Clinical Development, Berlin, Germany

7Charité – Universitätsmedizin Berlin, Medical Faculty, Berlin, Germany

Background

In the Phase III trial OASIS-4 (NCT05587296), elinzanetant (EZN), a dual neurokinin (NK)-targeted therapy (NK1 and NK3 receptor antagonist), significantly reduced vasomotor symptom (VMS) frequency vs placebo (PBO) in women taking endocrine therapy (ET) for hormone receptor positive (HR+) breast cancer. This subgroup analysis evaluated EZN’s effects on VMS frequency and severity by type of ET in OASIS-4.

Materials and methods

Women aged 18–70 years experiencing ≥35 moderate-to-severe VMS/week caused by ET for HR+ breast cancer were randomized 2:1 to receive EZN 120 mg for 52 weeks or PBO for 12 weeks followed by EZN for 40 weeks. Mean changes from baseline in daily moderate-to-severe VMS frequency and severity to weeks 1 (frequency only), 4 and 12 were analyzed by ET type (tamoxifen [TAM], aromatase inhibitor [AI], ovarian function suppression [OFS; i.e., GnRH], no OFS). This post hoc analysis was not powered for statistical testing.

Results

Mean age (years) was 50.4 for TAM, 51.9 for AI, 45.2 for OFS and 53.4 for no OFS. At baseline, mean average daily moderate-to-severe VMS frequency ranged from 10.8-12.5 per day while VMS severity was 2.5 in all subgroups. Greater reductions in VMS frequency with EZN vs PBO were seen by week 1 across all subgroups (range EZN: -3.3 to -4.2; PBO: -1.6 to -2.1), with further reductions at week 4 (range EZN: -5.6 to -6.9; PBO: -2.5 to -3.7) and 12 (range EZN: -6.9 to -8.1; PBO: -3.0 to -5.8). A similar trend was observed for VMS severity at weeks 4 and 12 (Table). Reductions in VMS frequency and severity were maintained throughout the 52-week treatment period.

Conclusions

Consistent with results in the overall population, EZN had greater reductions in VMS frequency and severity than PBO with rapid onset and sustained effect over 52 weeks, irrespective of the type of ET.

Fatima Cardoso MD at EBCC 2026 A J Oncology March 28, 2026

Elisabetta Bonzano MD PhD; 2025 EBCC: BRAVE-HEART Study Shows How Breath-Holding System Halves Coronary Radiation Dose During Left Breast Irradiation

Audio Medica News — Fri, 27 Mar 2026 14:51:31 +0000

BRAVE-HEART Study Shows How Breath-Holding System Halves Coronary Radiation Dose During Left Breast Irradiation

An interview with:

Elisabetta Bonzano MD PhD, IRCCS San Matteo Polyclinic Foundation, Radiation Oncology, Pavia, Italy

BARCELONA, Spain—A system known as Active Breathing Co-ordination had a large, consistent and significant effect in reducing radiation dose to the heart and left anterior descending coronary artery in the BRAVE HEART study led by radiation oncologists from Pavia in Italy.

Elisabetta Bonzano MD PhD, IRCCS San Matteo Polyclinic Foundation, Radiation Oncology, Pavia, Italy reported her group’s findings at the 2025 European Breast Cancer Conference. Afterwards she talked about more of the details for this edition of the Audio Journal of Oncology:

AUDIO JOURNAL OF ONCOLOGY: Elisabetta Bonzano MD PhD

IN: [GOODWIN]” Peter Goodwin here at the….

OUT: ………of Oncology, I’m Peter Goodwin. 5: 54 secs

EBCC Presentation number:PB-008

Abstract title:

BRAVE-HEART: Clinical and dosimetric validation of Active Breath Control for cardiac sparing in breast cancer radiotherapy

Bonzano1,, L. Squillace1,, A. Lancia1,, J. Saddi1,, S. Colombo1,, S. La Mattina1,, D.A. Santos1,, P. Pedrazzoli2,.

1IRCCS San Matteo Polyclinic Foundation, Radiation Oncology, Pavia, Italy.

2IRCCS San Matteo Polyclinic Foundation, Oncology, Pavia, Italy.

Background:

Cardiac exposure during left-sided breast cancer (LBC) radiotherapy remains a key determinant of long-term morbidity and mortality. The BRAVE-HEART trial explores the clinical and dosimetric impact of Deep Inspiration Breath Hold (DIBH) using the Active Breathing Coordinator (ABC) system. This analysis quantifies the cardiac-sparing effect of ABC versus free-breathing (FB) across three fractionation schedules, validates its intrinsic benefit through intra-patient paired replanning, and assesses real-world feasibility. (ClinicalTrials.gov awaiting release)

Methods:

This ambispective single-center study included 400 patients with early or locally advanced LBC treated with 26 Gy/5 fx, 40 Gy/15 fx, or 50 Gy/25 fx ± SIB. Dosimetric parameters were extracted for the heart and LAD (Dmean, Dmax). Statistical analyses used the Shapiro–Wilk, Mann–Whitney U, and Wilcoxon tests; effect size was reported as Cohen’s d. Model-based estimation of cardiac mortality risk (NTCP) was performed for the replanning subgroup using the Gagliardi relative-seriality model. For this subgroup, paired FB and ABC-DIBH plans were generated on separate CT scans. Breath-hold performance (hold duration, threshold volume) was recorded to evaluate feasibility. The study was approved by the Ethics Committee of the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Results:

ABC significantly reduced cardiac and LAD exposure across all fractionations (all p < 0.001), with large effect sizes (Cohen’s d ≥0.8) indicating a strong clinical impact (Tab. 1). In intra-patient replanning, ABC confirmed its dosimetric superiority over FB (p < 0.05). Model-based NTCP for late cardiac mortality showed a halving of predicted cardiac risk with ABC (0.04 vs 0.08, p < 0.001). Breath-hold metrics confirmed high feasibility (mean DIBH ≈ 25 s; threshold ≈ 1.4 L), including in elderly patients (mean age 75 years).

Conclusions:

ABC-assisted DIBH consistently and significantly reduced cardiac and coronary exposure across all dose regimens, with high reproducibility and feasibility. Model-based NTCP and intra-patient replanning analyses demonstrate a clinically and biologically relevant reduction in predicted long-term cardiac mortality, confirming ABC-DIBH as a reliable strategy to improve cardiac safety in left-sided breast cancer radiotherapy.

Elisabetta Bonzano MD PhD

Philip Poortmans MD PhD; 2026 EBCC: European Breast Cancer Conference: Focus on Therapy De-escalation and Individualization

Audio Medica News — Fri, 27 Mar 2026 13:50:31 +0000

European Breast Cancer Conference: Focus on Therapy De-escalation and Individualization

An interview with:

Philip Poortmans MD PhD, Radiation Oncology Department, University of Antwerp & Iridium Netwerk, Belgium

BARCELONA, Spain—One of the important themes at the 2026 European Breast Cancer Conference was to individualize therapy for every patient by de-escalating some modalities of treatment in the light of the increasing efficacy of others. The Audio Journal of Oncology sought the opinion of one of Europe’s oncology leaders, Philip Poortmans MD, PhD, researcher at the Iridium Netwerk and the University of Antwerp, in Belgium about findings from the EUROPA trial looking at older patients with early breast cancer, new date on omitting radiation boost to the tumor bed after breast conserving therapy, using axillary radiotherapy in place of axillary node dissection, and the case for watchful waiting in more patients with DCIS.

AUDIO JOURNAL OF ONCOLOGY PODCAST: Philip Poortmans MD PhD

IN: [GOODIN] “Now, Philip Poortmans is …..

OUT: …….of Oncology, I’m Peter Goodwin 11:57secs

Philip Poortmans MD PhD A J Oncology EBCC 2026

Tess Snellen MD; 2026 EBCC: Molecular Test Distinguishes Ipsilateral Second Primary from Recurrent Breast Cancer

Audio Medica News — Wed, 25 Mar 2026 15:43:04 +0000

Molecular Test Distinguishes Ipsilateral Second Primary from Recurrent Breast Cancer

An interview with:

Tess Snellen MD, Netherlands Cancer Institute – Antoni van Leeuwenhoek hospital, Department of Surgical Oncology, Amsterdam, The Netherlands.

BARCELONA, Spain—A molecular test using next generation sequencing has proved able to distinguish swiftly, and with great accuracy, the recurrence of a patient’s ipsilateral breast cancer from a completely new primary tumor. The 2026 European Breast Cancer Conference heard findings from researcher Tess Snellen from the Netherlands Cancer Institute in Amsterdam, who then talked with our reporter, Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Tess Snellen MSc

EBCC 2026 ABSTRACT:

Distinguishing True Recurrence from Second Primary Breast Cancer by Molecular Clonality Analysis

Snellen1,, E. Lips2,, L. Bosch3,, T. Wiersma4,, A. Scholten4,, M. Noë5,, M.J. Vrancken Peeters6,, V. Dezentjé7,.

1Netherlands Cancer Institute – Antoni van Leeuwenhoek hospital, Department of Surgical Oncology, Amsterdam, The Netherlands.

Background

A second breast cancer (BC) in the ipsilateral breast or regional lymph nodes may be a true recurrence (TR) or second primary (SP) tumor. This distinction is clinically relevant, as TRs are associated with a poorer prognosis and require a more challenging therapeutic approach compared to SPs. The aim of this study was to describe the findings and success rates of molecular clonality analysis (MCA) techniques used to distinguish a second ipsilateral BC as either a TR or a SP. In addition, a comparison between a MCA-based and a clinicopathological classification was made.

Material and methods

Through electronic patient files and pathology reports, data were collected from a historical cohort of patients who underwent MCA for a second ipsilateral locoregional BC at the Netherlands Cancer Institute between 2000 and 2024. The primary objective was to describe the findings and success rates of the different MCA techniques. The secondary objective was to compare molecular with clinicopathological classification using the Jobsen Morphology method.

Results

In total, 85 patients were included, in whom 99 MCAs were performed. Before 2017, all MCA involved loss of heterozygosity (LOH) analysis (100%), hereafter, targeted next-generation sequencing (NGS) panel analysis and copy number variation (CNV) analysis were introduced. After 2017, targeted NGS panel analysis was most frequently applied (65.4%), followed by CNV (18.5%) and LOH analysis (16.0%). CNV analysis had the highest success rate (93.3%) yielding the most conclusive MCA results, followed by targeted NGS panel (73.6%), and LOH analysis (61.3%) (table 1). Of the 99 MCAs, 40.4% tumor pairs were classified as clonally related, 10.1% as likely clonally, 22.2% as not clonally related, 27.3% were inconclusive. A substantial discordance (29.6%) was observed between the MCA-based classification and Jobsen Morphology method, with clinicopathological assessment showing limited predictive value for MCA-determined TRs (PPV 78.7%, NPV 22.2%).

Conclusion

In conclusion, we demonstrate that MCA, especially targeted NGS panel and CNV analysis, is successful in distinguishing TRs from NPs. Clinicopathological classification using the Jobsen Morphology method however has limited value in predicting clonal relatedness. Therefore, we recommend implementing MCA in the diagnostic workup of second ipsilateral BC when the outcome may influence therapeutic decision-making, as part of a tailored treatment approach for BC recurrence.

260325 Tess Snellen EBCC 2026 Audio Journal of Oncology

Charles E Geyer MD; ESMO 2025: Antibody Drug Conjugate T-DXd Brings Longer Cancer-Free Survival for Patients with HER2-Positive Early Breast Cancer and Residual Invasive Disease

Audio Medica News — Fri, 20 Mar 2026 12:08:47 +0000

Antibody Drug Conjugate T-DXd Brings Longer Cancer-Free Survival for Patients with HER2-Positive Early Breast Cancer and Residual Invasive Disease

An interview with:

Charles E Geyer MD, Breast Medical Oncologist, University of Pittsburgh Hillman Cancer Center, Pittsburgh USA, Chief Scientific Officer, NSABP Foundation.

BERLIN, Germany— The antibody drug conjugate trastuzumab deruxtecan (T-DXd) was found to bring improved disease-free survival among patients with high-risk HER2-positive primary breast cancer who had residual invasive disease after neoadjuvant therapy, compared to a control group of patients who were treated with trastuzumab emtansine (T-DM1) after the same neoadjuvant therapy.

This was reported in an interim analysis of the DESTINY-Breast05 study at the European Society for Medical Oncology Annual Congress in Berlin by lead author Charles Geyer MD, Breast Medical Oncologist at the University of Pittsburgh Hillman Cancer Center in Pittsburgh, USA, who is also Chief Scientific Officer for the NSABP Foundation. After the conference he talked with the Audio Journal of Oncology’s Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Charles E Geyer MD

IN: [GOODWIN]”Welcome to the Audio Journal of Oncology….

OUT: ……Oncology, I’m Peter Goodwin” 21:18secs

ESMO 2025 Abstract:

LBA1 – Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with high-risk human epidermal growth factor receptor 2–positive (HER2+) primary breast cancer (BC) with residual invasive disease after neoadjuvant therapy (tx): Interim analysis of DESTINY-Breast05

https://www.annalsofoncology.org/article/S0923-7534(25)04791-X/fulltext

Speakers

Charles E. Geyer (Pittsburgh, United States of America)

Authors

Charles E. Geyer (Pittsburgh, United States of America) Yeon Hee Park (Seoul, Republic of Korea) Zhi-Ming Shao (Shanghai, China) Chiun-Sheng Huang (Taipei City, Taiwan) Carlos H. Barrios (Porto Alegre, Brazil) Jame Abraham (Cleveland, United States of America) Aleix Prat (Barcelona, Spain) Naoki Niikura (Kanagawa, Japan) Michael Untch (Berlin, Germany) Seock-Ah Im (Seoul, Republic of Korea) Wei Li (Changchun, China) Huiping Li (Beijing, China) Yongsheng Wang (Jinan, China) Herui Yao (Guangzhou, China) Sung-Bae Kim (Seoul, Republic of Korea) Elton Mathias (Basking Ridge, United States of America) Yuta Sato (Shinagawa-ku, Japan) Wenjing Lu (Basking Ridge, United States of America) Hanan Abdel-Monem (Basking Ridge, United States of America) Sibylle Loibl (Neu-Isenburg, Germany)

Abstract

Background

Pts with HER2+ early BC with residual invasive disease after neoadjuvant tx are at high risk of recurrence highlighting a significant unmet need. We present interim analysis results of DESTINY-Breast05 (NCT04622319), an open-label, phase 3 trial of post-neoadjuvant T-DXd vs standard of care (SOC) T-DM1 in HER2+ early BC.

Methods

Pts with residual invasive HER2+ BC after neoadjuvant tx consisting of taxane-based chemotherapy and anti-HER2 tx and at high risk for recurrence* were randomized 1:1 to T-DXd 5.4 mg/kg or T-DM1 3.6 mg/kg once every 3 weeks for 14 cycles. Primary endpoint was IDFS. Key secondary endpoint was DFS; others were overall survival, distant recurrence-free interval, brain metastasis–free interval (BMFI), and safety.

Results

At data cutoff (July 2, 2025), 1635 pts were randomized to T-DXd (n = 818) or T-DM1 (n = 817). Median study duration was 29.9 months with T-DXd and 29.7 months with T-DM1. IDFS and DFS benefit with T-DXd vs T-DM1 was statistically significant (HR, 0.47 each; Table); BMFI improvement with T-DXd was clinically meaningful (HR, 0.64; 95% CI, 0.35-1.17). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 50.6% of pts with T-DXd and 51.9% of pts with T-DM1; adjudicated drug-related interstitial lung disease occurred in 9.6% (n = 2 grade 5) and 1.6% of pts (0 grade 5) and were mostly grade 1 or 2. TEAEs associated with death occurred in 0.4% (n = 3) and 0.6% (n = 5) of pts, respectively. Table: LBA1

Efficacy summary at interim analysis (data cutoff, July 2, 2025)

Efficacy T-DXd n = 818 T-DM1 n = 817 HR (95% CI)

IDFS Patients with events, n (%) 51 (6.2) 102 (12.5) 0.47 (0.34-0.66); P † = <0.0001

DFS Patients with events, n (%) 52 (6.4) 103 (12.6) 0.47 (0.34-0.66); P † = <0.0001

DFS, disease-free survival; HR, hazard ratio; IDFS, invasive disease-free survival.*Defined as clinical stages T4, N0-3, M0 or T1-3, N2-3, M0 at presentation (prior to neoadjuvant therapy) or clinical stages T1-3, N0-1, M0, with axillary node-positive disease (ypN1-3) following neoadjuvant therapy.†Stratified log rank.

Conclusions

T-DXd showed a statistically significant and clinically meaningful IDFS and DFS benefit vs T-DM1, extending its superiority to post-neoadjuvant residual disease in pts with HER2+ early BC, and representing a potential new SOC. Safety of T-DXd was generally manageable with no new safety signals.

AUDIO JOURNAL OF ONCOLOGY March 19, 2025: Charles Geyer

Hope S. Rugo, MD; SABCS 2025: Selective Estrogen Degrader Giredestrant Brings Clinically Meaningful Improvements in Metastatic Breast Cancer: evERA Breast Cancer Trial

Audio Medica News — Fri, 06 Mar 2026 14:58:25 +0000

Hope S. Rugo, MD; SABCS 2025: Selective Estrogen Degrader Giredestrant Brings Clinically Meaningful Improvements in Metastatic Breast Cancer: evERA Breast Cancer Trial

An interview with:

Hope S. Rugo, MD, Director, Women’s Cancers Program; Division Chief, Breast Medical Oncology; Professor, Department of Medical Oncology and Therapeutic Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA

SAN ANTONIO, USA—Further improvements in hormone therapy for ER-positive breast cancer were on display at the San Antonio Breast Cancer Symposium where results from the Phase III evERA Breast Cancer trial were discussed. The study investigated the use of the selective estrogen degrader agent giredestrant used together with everolimus in patients with estrogen receptor-positive, HER2-negative advanced breast cancers that had previously been treated with a CDK4/6 inhibitor.

Hope S. Rugo, MD, Division Chief of Breast Medical Oncology at the City of Hope Comprehensive Cancer Center in Duarte, California, delivered the latest findings at the conference. Afterwards she talked with Peter Goodwin from the Audio Journal of Oncology.

Audio Journal of Oncology: Hope S. Rugo

IN: [GOODWIN]”Peter Goodwin here with the ….

OUT: …..thank you so much! Bye! 11:40 secs

San Antonio Breast Cancer Symposium, Abstract GS3-09:

Clinical and biomarker subgroup analysis of evERA Breast Cancer: A Phase III trial of giredestrant plus everolimus in patients with estrogen receptor-positive, HER2-negative advanced breast cancer previously treated with a CDK4/6 inhibitor.

S. Rugo; S. M. Tolaney; K. L. Jhaveri; M. Martin; G. A. Vidal; L. Moscetti; A. Brufsky; W. J. Gradishar; A. Schneeweiss; N. Niikura; A. Favret; M. Alfie; K. S. Lee; S. Khan; M. Feldman; B. M. Day; L. H. Lam; W. C. Darbonne; T. M. Fernando; P. Perez-Moreno; E. L. Mayer

Background

The first-line standard of care (SOC) for patients (pts) with estrogen receptor-positive, HER2-negative advanced breast cancer (ER+, HER2- aBC) is CDK4/6 inhibitor (i) + endocrine therapy (ET) but effective post-CDK4/6i options remain limited. Giredestrant (GIRE) targets the ER pathway while everolimus (E) targets the PI3K/AKT/mTOR pathway; both of which are implicated in driving resistance in the post-CDK4/6i setting. evERA BC (NCT05306340) is the first Phase III trial to demonstrate statistically significant and clinically meaningful improvement in investigator-assessed progression-free survival (INV-PFS) with an all-oral selective ER antagonist and degrader combination of GIRE + E vs SOC ET + E in pts with ER+, HER2- aBC post-CDK4/6i + ET, both in pts whose tumors had a detectable ESR1 mutation (m) and in the intent-to-treat (ITT) population (Mayer ESMO 2025). The safety profile of GIRE + E was manageable with no unexpected findings (Mayer ESMO 2025). We report results from prespecified exploratory subgroup analyses.

Methods

Pts who had ER+, HER2- aBC with disease progression (PD) post-CDK4/6i + ET in the aBC setting, or relapse during/after CDK4/6i + ET in the adjuvant setting, were randomized 1:1 to once-daily oral 30 mg GIRE + 10 mg E or SOC ET (exemestane, fulvestrant, or tamoxifen) + E until PD or unacceptable toxicity. Mutational status was determined using circulating tumor DNA at baseline. The co-primary endpoints were INV-PFS per Response Evaluation Criteria in Solid Tumors v1.1 in pts whose tumors had detectable ESR1m and in the ITT population. INV-PFS was assessed by subgroup analyses.

Results

Three-hundred-and-seventy-three pts were randomized; 183 pts were randomized to GIRE + E and 190 to SOC ET + E. A total of 207 pts (55%) had tumors with ESR1m, 115 (31%) had PIK3CAm, and 137 (37%) had alterations (alt) in the PI3K pathway genes (PIK3CA/AKT1/PTEN). Sixty-four pts (17%) had both ESR1m and PIK3CAm; 76 (20%) had both ESR1m and PIK3CA/AKT1/PTEN alt. Ninety-eight percent of pts received a CDK4/6i in the metastatic setting. INV-PFS benefit was observed for GIRE + E vs SOC ET + E regardless of PIK3CAm status or PIK3CA/AKT1/PTEN alt in both the ESR1m and ITT populations (Table). Consistent benefit was observed regardless of duration of prior CDK4/6i (Table). Data for additional subgroup analyses for prior therapy will be presented.

Conclusions

GIRE + E led to clinically meaningful improvements in INV-PFS vs SOC ET + E irrespective of PIK3CAm and PIK3CA/AKT1/PTEN alt, and other key relevant subgroups, regardless of ESR1m status. These data support the use of GIRE + E vs SOC ET + E in pts with ER+, HER2- aBC post-CDK4/6i + ET.

Audio Journal of Oncology March 6th , 2026.

Othman Al-Sawaf MD PhD; ASH 2025: Fixed-Duration Targeted Combinations As Effective as Extended Monotherapy for Patients with Untreated Chronic Lymphocytic Leukemia

Audio Medica News — Mon, 02 Mar 2026 12:20:21 +0000

Othman Al-Sawaf MD PhD; ASH 2025: Fixed-Duration Targeted Combinations As Effective as Extended Monotherapy for Patients with Untreated Chronic Lymphocytic Leukemia

An interview with:

Othman Al-Sawaf MD PhD, Hematologist & Medical Oncologist, University Hospital of Cologne, Department I of Internal Medicine, Cologne, Germany

ORLANDO, USA— Early data from the CLL17 international, randomized phase three trial for patients with previously untreated chronic lymphocytic leukemia found that fixed-duration treatment with either venetoclax plus obinutuzumab or venetoclax plus ibrutinib were non-inferior to continuous treatment with ibrutinib and may therefore become the preferred treatment option.

Othman Al-Sawaf MD PhD, who is a hematologist & medical oncologist, University Hospital of Cologne’s, Department I of Internal Medicine in Cologne, Germany, reported the findings at the 2025 Annual Meeting of the American Society of Hematology. After his talk he met up with Audio Journal of Oncology reporter Peter Goodwin:

Audio Journal of Oncology: Othman Al-Sawaf MD PhD

IN: [GOODWIN]”The Audio Journal of Oncology…..

OUT: …….I’m Peter Goodwin” 8:15 secs

ASH 2025 ABSTRACT

Fixed-duration versus continuous targeted treatment for previously untreated chronic lymphocytic leukemia: Results from the randomized CLL17 trial

AUTHORS:

Othman Al-Sawaf, Janina Stumpf, Can Zhang, Florian Simon, Francesc Bosch Albareda, Emadoldin Feyzi, Paolo Ghia, Michael Gregor, Arnon Kater, Vesa Lindström, Mattias Mattsson, Carsten Niemann, Philipp Staber, Tamar Tadmor, Patrick Thornton, Clemens-Martin Wendtner, Ann Janssens, Thomas Noesslinger, Jan-Paul Bohn, Caspar da Cunha-Bang, Christian Poulsen, Juha Ranti, Thomas Illmer, Bjoern Schoettker, Sebastian Böttcher, Tobias Gaska, Elisabeth Vandenberghe, Ruth Clifford, Ohad Benjamini, Annamaria Frustaci, Lydia Scarfo, Paolo Sportoletti, John Schreurs, Mark-David Levin, Hanneke van der Straaten, Marjolein van der Klift, Hoa Tran, Javier de la Serna, Javier Loscertales, Oscar Lindblad, Anna Bergendahl Sandstedt, Jeroen Goede, Michael Baumann, Anna Maria Fink, Kirsten Fischer, Matthias Ritgen, Karl-Anton Kreuzer, Christof Schneider, Eugen Tausch, Stephan Stilgenbauer, Sandra Robrecht, Barbara Eichhorst, Michael Hallek

Blood (2025) 146 (Supplement 1): 1.

https://doi.org/10.1182/blood-2025-1

https://ashpublications.org/blood/article/146/Supplement%201/1/553644/Fixed-duration-versus-continuous-targeted

Introduction

Current treatment for chronic lymphocytic leukemia (CLL) follows two seminal paradigms: continuous Bruton tyrosine kinase inhibitor (BTKi) therapy until progression and fixed-duration regimens combining BCL2 inhibitors with a CD20 antibody or BTKi, typically given over one year. These two different approaches were established through comparisons to chemo(immuno)therapy and are yet to be compared directly. Here we present data of a prospective trial comparing continuous ibrutinib (I) monotherapy to fixed-duration venetoclax plus obinutuzumab (VO) and venetoclax plus ibrutinib (VI) for CLL.

Methods

CLL17 (NCT04608318) is an investigator-initiated, international, randomized phase 3 trial for patients (pts) with previously untreated CLL. Pts were randomized to receive ibrutinib (I), fixed-duration venetoclax plus obinutuzumab (VO) or fixed-duration venetoclax plus ibrutinib (VI). Randomization was stratified by IGHV status, del(17p)/TP53mut and patient fitness, defined by cumulative illness rating scale (CIRS) score >6 and/or creatinine clearance <70 mL/min.

Ibrutinib was given continuously until intolerance or progression; VO consisted of 6 cycles (28 days each) of venetoclax plus obinutuzumab, followed by 6 additional cycles of venetoclax monotherapy; VI was initiated with a 3-cycle ibrutinib lead-in, followed by 12 cycles of VI.

The study was designed to test non-inferiority of VO vs I and VI vs I. The primary endpoint was investigator-assessed progression-free survival (PFS). A ≤8% reduction in 3-year (yr) PFS was deemed not clinically meaningful (non-inferiority HR margin 1.608). Per protocol, an interim analysis was planned once 65% of required PFS events (138 of 213) were reached. Secondary endpoints included overall response rate (ORR), undetectable minimal residual disease (uMRD), overall survival (OS) and safety.

Results

In total, 909 pts were randomized to VO (N=303), VI (N=305), and I (N=301). Data cut-off was on April 11th, 2025, median observation time was 34.2 months (range 0-49). Median age was 66 yrs (34-90), 67.8% were male, median CIRS score was 3 (0-18); 33.7% had a creatinine clearance <70 mL/min. Overall, 7.6% had del(17p) and/or TP53 mutation, 56.5% unmutated IGHV and 19.2% complex karyotype (≥3 aberrations); 53.8% and 6.5% had high or very high CLL-IPI, respectively.

Three-yr PFS was 81.1% in the VO arm compared to 81.0% in the I arm (HR 0.87, type-I-error adjusted CI [98.3%] 0.54-1.41) and 79.4% in the VI arm (compared to I arm: HR 0.84, type-I-error adjusted CI [98.0%] 0.53-1.32), respectively, with the upper limit of each adjusted CI below the pre-defined non-inferiority margin, providing early evidence of non-inferiority.

At final staging (C18D1), the ORR was 84.2% in the VO arm, 88.5% in the VI arm, and 86.0% in the I arm, with a CR rate of 51.5%, 46.2%, and 8.3%, respectively; the uMRD (<10-4) rate in ITT population in peripheral blood was 73.3% (62.0% in bone marrow) in the VO arm, 47.2% (40.0% in bone marrow) in the VI arm and 0% (0% in bone marrow) in the I arm.

At 3 yrs, the OS rate was 91.5% in the VO arm, compared to 95.7% in the I arm (HR 1.67, 95% CI 0.86-3.28) and 96.0% in the VI arm (compared to I: HR 0.96, 95%CI 0.45-2.05), respectively.

For pts with unmutated IGHV, 3-yr PFS in the VO arm was 75.8% (87.6% for mutated IGHV) compared to 79.7% (83.5%) in the I arm (HR 0.98, 95% CI 0.61-1.59), and 78.9% (80.0%) in the VI arm (compared to I: HR 0.81, 95% CI 0.49-1.32). For pts with del(17p)/TP53mut, 3-yr PFS in the VO arm was 62.0% (82.7% for pts without del(17p)/TP53mut) compared to 79.4% (81.0%) in the I arm (HR 1.20, 95% CI 0.40-3.59), and 69.0% (80.1%) in the VI arm (compared to I: HR 0.70, 95% CI 0.22-2.16).

The most frequent AEs were infections and infestations (VO: 76.3%, VI: 80.2%, I: 79.9%), gastrointestinal disorders (VO: 59.7%, VI: 74.3%, I: 63.4%), and blood and lymphatic system disorders (VO: 59.0%, VI: 42.9%, I: 28.5%). Covid-19 infection was reported in 38.3%, 42.2% and 39.3% of pts; cardiac disorders occurred in 13.9%, 23.8% and 34.6% of pts; second cancers were reported in 11.5%, 11.2% and 18.5% of pts, respectively.

Conclusion

This is the first phase 3 trial comparing the main paradigms of continuous vs fixed-duration targeted therapy of CLL. Early findings indicate that fixed-duration treatment with VO or VI are non-inferior to continuous treatment with I and may therefore represent the preferred treatment option for pts with previously untreated CLL.

Audio Journal of Oncology ASH 2025: Othman Al-Sawaf MD PhD

March 2, 2026

Juan Du MD PhD, ASH 2025: Dual Targeted FasTCAR-T Therapy brings Deep, Durable Responses to Patients with Newly Diagnosed Multiple Myeloma

Audio Medica News — Mon, 23 Feb 2026 13:43:14 +0000

Juan Du MD PhD, ASH 2025: Dual Targeted FasTCAR-T Therapy brings Deep, Durable Responses to Patients with Newly Diagnosed Multiple Myeloma

An interview with:

Juan Du MD PhD, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

ORLANDO, USA—Patients with newly diagnosed multiple myeloma had deep, long lasting responses to initial therapy with a new CAR T-cell therapy targeting both B-cell maturation antigen (BCMA) and CD19 using the “FasTCAR-T” platform being tested in a phase one study. Lead author Juan Du MD PhD, from Ren Ji Hospital, and Jiao Tong University School of Medicine, in Shanghai, China reported early findings to the 2025 Annual Meeting of the American Society of Hematology. Afterwards she met up with the Audio Journal of Oncology’s Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY, Juan Du MD PhD

https://ashpublications.org/blood/article/146/Supplement%201/258/548757/A-dual-targeting-BCMA-and-CD19-fastcar-t-GC012F

A dual targeting BCMA and CD19 fastcar-t (GC012F/AZD0120) as first-line therapy for newly diagnosed multiple myeloma

REFERENCE:

Blood (2025) 146 (Supplement 1): 258.

AUTHORS:

Juan Du, Wanting Qiang, Jing Lu, Yanchun Jia, Haiyan He, Jin Liu, Pei Guo, Ying Yang, Zhongyuan Feng, Lina Jin, Xiaoqiang Fan, Nina Shah, Qi Zhang, Lianjun Shen, Jia Liu

ASTRACT:

Background

GC012F/AZD0120 is an autologous CAR-T therapy that targets both B cell maturation antigen (BCMA) and CD19. It is developed using the novel FasTCAR-T platform, which allows for next-day manufacturing. GC012F/AZD0120 has demonstrated deep and durable responses with a manageable safety profile in relapsed/refractory multiple myeloma (RRMM) patients (pts). We conducted two phase 1, open-label, investigator-initiated trials (NCT04935580, NCT05840107) to evaluate safety and efficacy of GC012F/AZD0120 in newly diagnosed multiple myeloma (NDMM) pts, including transplant eligible high risk (TE HR) NDMM and transplant ineligible (TI) NDMM. Here, we report the combined data of these two studies to provide long term follow up data of GC012F/AZD0120 in NDMM pts.

Methods

Eligible NDMM pts received a single infusion of GC012F/AZD0120 following two cycles lenalidomide, bortezomib and dexamethasone (RVd) induction therapy. Leukapheresis was performed before induction therapy, or after 1 or 2 cycles of induction therapy. GC012F/AZD0120 was administered at 4 dose levels: 1×105/kg (n=1), 1.5×105/kg (n=3), 2×105/kg (n=4), or 3×105/kg (n=22) after a standard 3-day lymphodepletion regimen of fludarabine and cyclophosphamide. Lenalidomide maintenance was permitted to be administered post infusion per investigator’s discretion.

Results

As of June 3, 2025, a total of 30 patients were infused and evaluable. The median age was 64 years (range, 43-78), with 27% aged over 70 years. 19 pts (63%) were male. 25 pts (83%) had R-ISS stage II/III and 14 of 29 pts (48%) had high risk cytogenetics (dep (17p), amp (1q21), t (4;14), t (14;16)). 17 pts (57%) had plasmacytomas, and 3 of them had soft tissue plasmacytomas. 29 pts (97%) received 2 cycles of RVd induction therapy prior to CAR-T infusion. The overall response rate (ORR) was 100%, and the stringent complete response (sCR) rate was 97%. The median time to first response was 28 days and the median time to best response was 68 days. All treated pts (100%) across all dose levels achieved minimal residual disease (MRD) negativity, as assessed by Euroflow (sensitivity of 10-6). Among MRD evaluable pts, MRD negativity reached 100%, 93% and 92% at Month 1, Month 6 and Month 12, respectively. 81.5% (22/27) pts’ MRD negativity sustained more than 12 months. With a median follow-up of 30 months (range, 13-47), the median progression-free survival (PFS) and overall response (OS) have not been reached. The 30-month PFS rate was 88% (95% CI 67–96) and 30-month OS rate was 92% (95% CI 71–98). For 3 soft tissue plasmacytomas pts, the median PFS was 17.9 months and the median OS was 20.8 months, significantly shorter than bone related plasmacytomas and non-plasmacytomas pts. No difference was observed between pts with high risk and non-high-risk cytogenetics. GC012F/AZD0120 was well tolerated. Cytokine release syndrome (CRS) occurred in 10 pts (33%), all grade 1–2 (grade 1, n=9; grade 2, n=1); no grade ≥3 CRS was observed. The median time to onset was 8 (range, 6-18), with a median duration of 2 days (range, 1-8). 3 pts were treated with one dose of tocilizumab and 1 pt was treated with one dose of tocilizumab and corticosteroids. No patient developed ICANS of any grade. Robust CAR T-cell expansion was observed in all pts, with a median peak expansion (Cmax) of 62,644 copies /μg DNA and a median Tmax of 10 days. The median Tlast was 29 days. sBCMA level declined sharply post infusion, reaching to nadir with a median time of 2 months. 23 pts (77%) received lenalidomide as maintenance treatment, with a median initiation time of 6 months post infusion.

Conclusion

Consistent with findings from the previous relapsed/ refractory MM cohort treated with GC012F/AZD0120, data from these two studies demonstrates that GC012F/AZD0120 induced deep and durable responses in NDMM pts, with a highly favorable safety profile. All patients responded (100% ORR) and all four dose groups achieved MRD negativity. These promising results highlight the potential of GC012F/AZD0120 CAR-T therapy for treating NDMM patients with HR features and transplant ineligible NDMM pts. Further research with a larger patient population and extended follow-up is needed to validate these findings and address this critically unmet medical need.

Juan Du MD PhD 2025 SABCS Audio Journal of Oncology Text

Thorsten Kühn MD PhD; SABCS 2025: No Need for Axillary Node Dissection When Clinically Node-Positive Breast Cancers Convert to Node-Negative After Neoadjuvant Chemotherapy

Audio Medica News — Thu, 19 Feb 2026 21:36:33 +0000

Thorsten Kühn MD PhD; SABCS 2025: No Need for Axillary Node Dissection When Clinically Node-Positive Breast Cancers Convert to Node-Negative After Neoadjuvant Chemotherapy

An interview with:

Thorsten Kühn MD PhD, Head, Breast Center, Filderklinik, Stuttgart, Germany; Senior Consultant, University of Ulm; Chairman, European Breast Cancer Research Association of Surgical Trialists

SAN ANTONIO, USA— Breast cancers that convert from clinically node-positive to node-negative as a result of neoadjuvant chemotherapy, do not need axillary lymph node dissection, regardless of tumor type.

Less invasive axillary surgical staging procedures (such as sentinel node dissection and targeted axillary dissection) were just as good in terms of three-year outcomes, regardless of initial tumor stage or subtype, in findings from the international, prospective, multicenter AXSANA/EUBREAST 3 (R) study reported at the 2025 San Antonio Breast Cancer symposium by Thorsten Kühn MD PhD, Head of the Breast Center at the Filderklinik near Stuttgart, Germany, Senior Consultant, at the University of Ulm and Chairman of the European Breast Cancer Research Association of Surgical Trialists. At the symposium he gave more details to Audio Journal of Oncology reporter, Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY, Thorsten Kühn

IN: [GOODWIN]”I’m at the San Antonio……

OUT: ……of Oncology, I’m Peter Goodwin 9:29secs

SABCS Abstract GS2-01

TITLE:

“More versus less invasive axillary surgical staging procedures in breast cancer patients converting from a clinically node-positive to a clinically node-negative stage through neoadjuvant chemotherapy – primary endpoint analysis of the international prospective multicenter AXSANA/EUBREAST 3(R)study“

AUTHOR:

Thorsten Kühn MD PHD, Die Filderklinik gGmbH / University of Ulm, Ulm, Germany

Introduction:

In breast cancer patients converting from clinically positive (cN+) to negative (ycN0) lymph node status after neoadjuvant chemotherapy (NACT), surgical staging by axillary lymph node dissection (ALND) is increasingly replaced by less invasive procedures like targeted axillary dissection (TAD) or sentinel lymph node biopsy (SLNB), possibly followed by completion ALND or regional radiotherapy if positive. Prospective data comparing oncologic safety of different procedures as a primary approach after NACT are currently scarce. We report 3-year axillary recurrence-free survival (ARFS) as the first primary endpoint analysis of the AXSANA/EUBREAST 3(R) study (NCT04373655, www.eubreast.org/axsana), initiated by the European Breast Cancer Research Association of Surgical Trialists (EUBREAST e.V.).

Methods

In an international multicenter cohort study, patients with cN+ breast cancer who receive at least four cycles of NACT and convert to ycN0 are eligible. Axillary staging after NACT is performed according to institutional routine. Grouping of patients was based on the primary staging procedure, not on final axillary surgery, e.g., completion ALND following a positive SLNB was classified as SLNB. Co-primary endpoints are ARFS, invasive breast cancer-specific survival (iBCSS), and patient-reported quality of life. Data entry is systematically monitored. Less extensive axillary staging procedures as first surgery after NACT (TAD, SLNB, targeted lymph node biopsy (TLNB)) are considered non-inferior to staging by ALND if the lower bound of a two-sided 90% confidence interval (CI) around 3-year ARFS exceeds 97%. 750 patients were required per group (TAD/SLNB/TLNB vs ALND).

Results

From June 2020 to April 2025, 6,474 patients (26 countries, 288 study sites) were enrolled, 2,632 of whom had completed surgery by December 31, 2023 and were selected for analysis. Primary staging procedure was ALND in 799 patients (30.4%) and less invasive procedures (419 SLNB, 1399 TAD, 15 TLNB) in 1,833 (69.6%). Nodal complete pathological response was reported in 1,345 patients (51.1%): 423 (31.4%) after ALND and 922 (68.6%) after TAD/SLNB/TLNB. 2489 patients (94.6%) received post-NACT nodal radiotherapy: 759 (95.0%) after ALND and 1730 (94.4%) after TAD/SLNB/TLNB.

After a median follow-up of 2.0 years (range, 0.01-4.5), 15 axillary recurrences occurred after TAD/SLNB/TLNB and 4 after ALND (4.2 vs 2.5 events/1000 person-years, p=0.351). 3-year ARFS was 99.2% (95% CI 98.2-100.0) after ALND and 98.8% (95% CI 98.1-99.5) after TAD/SLNB/TLNB. For TAD/SLNB/TLNB, the lower bound of a 90% CI was 98.2%. After SLNB, 1 axillary recurrence occurred and 14 after TAD (1.2 vs 5.1 events/1000 person-years, p=0.132). Results

were similar upon controlling for clinicopathological risk factors and neoadjuvant treatment or exclusion of 143 patients without radiotherapy. iBCSS at 3 years was 85.7% (95% CI 82.6-89.0) for ALND and 88.2% (95% CI 86.0-90.3) for TAD/SLNB/TLNB.

Conclusion

In patients who convert from clinically node-positive to node-negative breast cancer, the AXSANA study showed that less invasive surgical staging procedures are associated with a low axillary recurrence rate, not inferior to ALND after 3 years, regardless of initial tumor stage or subtype. These findings reinforce efforts to minimize surgical morbidity without compromising oncologic outcomes.

260219 Thorsten Kühn SABCS 2025 A J Oncology Text

María-Victoria Mateos; ASH 2025: Unprecedented Survival Benefits with BCMA/CD3 Bispecific Antibody Teclistamab in Patients with Relapsed or Refractory Multiple Myeloma: Majestec-3 Study Findings

Audio Medica News — Fri, 13 Feb 2026 17:34:27 +0000

María-Victoria Mateos; ASH 2025: Unprecedented Survival Benefits with BCMA/CD3 Bispecific Antibody Teclistamab in Patients with Relapsed or Refractory Multiple Myeloma: Majestec-3 Study Findings

An interview with:

María-Victoria Mateos MD PhD, Hematologist and Myeloma Unit Director, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, and Instituto de Biología Molecular y Celular del Cáncer (Universidad de Salamanca-Consejo Superior de Investigaciones Científicas), CIBERONC, Salamanca, Spain.

ORLANDO, USA—Statistically significant improvements in progression-free and overall survival among patients with relapsed or refractory multiple myeloma were reported at the 2025 Annual Meeting of the American Society of Hematology. The addition of the B-cell maturation antigen/CD3 bispecific antibody teclistamab to standard second-line therapies, brought “clinically remarkable” benefits in the majestec-3 study.

The first author María-Victoria Mateos MD PhD, Hematologist and Myeloma Unit Director at the University Hospital of Salamanca in Spain, gave the details to Audio Journal of Oncology reporter, Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: María-Victoria Mateos MD PhD

IN: [GOODWIN] “Peter Goodwin here at the American …….

OUT: …..I’m Peter Goodwin 8:01 secs

From: ASH 2025

Publication Number: LBA-6

Abstract Title : Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or Bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): Results of majestec-3

https://ashpublications.org/blood/article/146/Supplement%202/LBA-6/556932/Phase-3-randomized-study-of-teclistamab-plus

María-Victoria Mateos

1Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Instituto de Biología Molecular y Celular del Cáncer (Universidad de Salamanca-Consejo Superior de Investigaciones Científicas), CIBERONC, Salamanca, Spain

Blood (2025) 146 (Supplement 2): LBA-6.

https://doi.org/10.1182/blood-2025-LBA-6

AUTHORS:

María-Victoria Mateos1, Nizar Bahlis2, Aurore Perrot3, Ajay Nooka4, Jin Lu5, Charlotte Pawlyn6, 7, Roberto Mina8, Gaston Caeiro9, Alain Kentos10, Vania

Hungria11, Donna Reece12, Ting Niu13, Anne Mylin14,Charlotte Hansen15, Raphael Teipel16, Britta Besemer17, Meletios Dimopoulos18, 19, Elena Zamagni20, 21,

Satoshi Yoshihara22, Kihyun Kim23, Chang-Ki Min24, Paulus Geerts25, Elena Van Leeuwen-Segarceanu26, Agata Tyczynska27, Juan Luis Reguera28, Magnus Johansson29, Markus Hansson30, Mehmet Turgut31,Mark Grey32, Surbhi Sidana33, Paula Rodriguez-Otero34, Joaquin Martinez-Lopez35, Hamza Hashmi36, Robin Carson37, Rachel Kobos38, Weili Sun39, Kristen Lantz37, Anne Seifert40, Debbie Briseno-Toomey41, Lisa O’Rourke37, Maria Rubin38, Diego Vieyra37, Lijuan Kang39, Luciano Costa42

INSTITUTIONS

1 Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Instituto de Biología Molecular y Celular del Cáncer (Universidad de Salamanca-Consejo Superior de Investigaciones Científicas), CIBERONC, Salamanca, Spain,

2 Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada, 3 Universite de Toulouse, Centre Hospitalier Universitaire, Service d’Hematologie,

IUCT Oncopole CRCT, Toulouse, France,

4 Emory University, Winship Cancer Institute, Atlanta, GA, United States,

5 Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China,

6 The Royal Marsden NHS Foundation Trust, London, United Kingdom,

7 The Institute of Cancer Research, London, United Kingdom,

8 Division of Hematology, Department of Molecular Biotechnology and Health Sciences, AOU Città della Salute e della Scienza di Torino, University of Torino, Torino, Italy,

9 Hospital Privado Centro Medico de Córdoba SA, Córdoba, Argentina,

10 Department of Hematology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium,

11 Clinica São Germano, São Paulo, Brazil, 12 Princess Margaret Cancer Centre, Toronto, ON, Canada,

13 Department of Hematology, West China Hospital, Sichuan University, Chengdu, China,

14 Department of Hematology, Rigshospitalet, Copenhagen, Denmark,

15 Department of Hematology, Odense University

Hospital, Odense, Denmark,

16 Medizinische Klinik und Poliklinik I Universitätsklinikum Carl Gustav Carus

an der Technischen Universität Dresden, Dresden, Germany,

17 Department of Internal Medicine II, University Tübingen, Tübingen, Germany,

18 Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece,

19 Department of Medicine, Korea University, Seoul, Korea, Rep. of South,

20 IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di

Ematologia “Seràgnoli”, Bologna, Italy,

21 Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy,

22 Department of Hematology, Hyogo Medical University Hospital, Nishinomiya,

Japan,

23 Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea, Dem. People´s Rep. of,

24 Department of Hematology, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea, Dem. People´s Rep. of,

25 Department of Internal Medicine, Isala Klinieken, Zwolle, Netherlands,

26 Department of Hematology, St. Antonius Hospital Nieuwegein, Nieuwegein, Netherlands,

27 Department of Hematology and Transplantology, Medical University of Gdansk; Department of Hematology and Transplantology, University Clinical Center, Gdansk, Poland,

28 Department of Hematology, University Hospital Virgen del Rocío, Instituto de Biomedicina de la Universidad de Sevilla, Seville, Spain,

29 Medicinkliniken, Sunderby Sjukhus, Luleå, Sweden,

30 Sahlgrenska University Hospital, Göteborg, Sweden,

31 Department of Internal Medicine, Division of Hematology, Ondokuz Mayis University, Samsun Türkiye,

32 The Lancashire Haematology Centre, Blackpool Teaching Hospitals NHS Foundation Trust, Blackpool Victoria Hospital, Blackpool, United Kingdom,

33 Stanford University School of Medicine, Palo Alto, CA, United States,

34 Cancer Center Clínica Universidad de Navarra, University of Navarra,

Pamplona, Spain,

35 Hematology Department, Hospital 12 de Octubre, i+12, Universidad Complutense, MIC, Centro Nacional de Investigaciones Oncológicas, CIBERONC, Madrid, Spain,

36 Memorial Sloan Kettering Cancer Center, New York, NY, United States,

37 Johnson & Johnson, Spring House, PA, United States,

38 Johnson & Johnson, Raritan, NJ, United States,

39 Johnson & Johnson, Los Angeles, CA, United States,

40 Johnson & Johnson, High Wycombe, United Kingdom,

41 Johnson & Johnson, Yorba Linda, CA, United States,

42 Division of Hematology and Oncology, University of Alabama at Birmingham,

Birmingham, AL, United States

ABSTRACT:

Introduction: In RRMM, increasing rates of pt attrition and decreasing durability of responses with each line of therapy (LOT) necessitate early treatment (tx) with the most effective therapies. Immunotherapies that are widely accessible across different MM tx settings have the potential to change the trajectory of RRMM.

Teclistamab (Tec), the first approved BCMA×CD3 bispecific antibody (BsAb) for heavily pretreated RRMM, provided deep, durable responses in MajesTEC-1, with improved efficacy and safety in earlier LOTs. Daratumumab (Dara), a standard-of-care (SoC) foundational CD38 targeted therapy with direct on-tumor activity, has been shown to deplete immunosuppressive T-cells and expand cytotoxic T-cells, creating an immune-permissive microenvironment for synergistic Tec-mediated killing of MM cells. MajesTEC-3 (NCT05083169) evaluates Tec-Dara vs SoC DPd/DVd in RRMM. We report initial results for this first phase 3 study of BsAb therapy in MM.

Methods: Eligible pts had 1-3 prior LOTs including a PI and lenalidomide (Len; pts with 1 prior LOT must have been Len-refractory) with progressive disease (PD) on or after the last LOT. Pts with prior BCMA-directed therapy or refractory to anti-CD38 were excluded; prior anti-CD38 exposure was permitted. Pts were randomized 1:1 to Tec-Dara or DPd/DVd. The Tec-Dara group received 28-day cycles (C) of Tec (1.5 mg/kg QW in C1-2 [C1 preceded by the approved step-up dose schedule]; 3 mg/kg Q2W in C3-6; and 3 mg/kg Q4W in C7+) with Dara; steroids were not required after C1 Day 8. Tec and Dara dosing were aligned with the approved Dara schedule. DPd/DVd were administered per approved schedules. Progression-free survival (PFS) by IRC was the primary endpoint; secondary endpoints included complete response or better (≥CR), overall response, minimal residual disease (MRD) negativity (10–5; next-generation sequencing), overall survival (OS), time to worsening of symptoms (MySIm-Q), and safety.

Results: 587 pts were randomized (Tec-Dara, n=291; DPd/DVd, n=296). Median (range) age was 64 (25-88) yrs, median number of prior LOTs was 2 (1-3). With 34.5-mo median follow-up, Tec-Dara significantly improved PFS vs DPd/DVd (HR, 0.17; 95% CI, 0.12-0.23; P<0.0001); mPFS was NR and 18.1 mo, and 36-mo PFS rate was 83.4% and 29.7%, respectively. PFS benefit was consistent across all prespecified and clinically relevant pt subgroups, including age ≥75 yrs, Len-refractory, high-risk cytogenetics, ≥60% bone marrow plasma cells, soft-tissue plasmacytomas, and anti-CD38 exposed. Significantly higher rates of ≥CR (81.8% vs 32.1%; OR, 9.56; 95% CI, 6.47-14.14), overall response (89.0% vs 75.3%; OR, 2.65; 95% CI, 1.68-4.18), and MRD-negativity (58.4% vs 17.1%; OR, 6.78; 95% CI, 4.53-10.15) were observed with Tec-Dara (P<0.0001). There were 45 deaths with Tec-Dara and 96 with DPd/DVd, primarily due to PD (4.6%; 20.3%). OS significantly favored Tec-Dara (HR, 0.46; 95% CI, 0.32-0.65; P<0.0001), including across all prespecified subgroups. The 36-mo OS rates were 83.3% and 65.0%, respectively and >90% of Tec-Dara pts alive at 6 mo were also alive at 30 mo. Median time to worsening of MM symptoms was NR with Tec-Dara vs 39.9 mo with DPd/DVd (HR, 0.50; 95% CI, 0.34-0.72; P=0.0002).

At data cutoff, 49.4% of pts remained on study tx (Tec-Dara, 71.0%; DPd/DVd, 28.3%). Median tx duration was twice as long with Tec-Dara vs DPd/DVd (32.4 vs 16.1 mo). Frequency of grade 3/4 (Tec-Dara, 95.1%; DPd/DVd, 96.6%) and grade 5 (7.8%; 6.2%) treatment-emergent adverse events (TEAEs), were comparable (safety set: Tec-Dara, n=283; DPd/DVd, n=290). Serious TEAEs occurred in 70.7% Tec-Dara and 62.4% DPd/DVd pts; tx discontinuations due to TEAEs were low (4.6% vs 5.5%). Any grade infections occurred in 96.5% and 84.1% of Tec-Dara and DPd/DVd pts, respectively; grade 3/4 infections occurred in 54.1% and 43.4%. New onset grade ≥3 infections decreased over time, coinciding with transition to Q4W dosing and supported by antimicrobial and Ig prophylaxis guidance. CRS rate was 60.1% (grade 1/2: 44.2%/15.9%) and ICANS was 1.1% with Tec-Dara.

Conclusion: We demonstrate the clinically remarkable and statistically significant PFS and OS benefits of Tec-Dara vs SoC triplets in RRMM, with 83.4% of Tec-Dara pts alive and progression-free at 3 yrs. Infections with Tec-Dara were well managed with established protocols. This highly effective, off-the-shelf, immunotherapy combination represents a new SoC for RRMM as early as first relapse.

María-Victoria Mateos MD PhD AJO TEXT 13 February, 2026

Erika Hamilton MD; 2025 SABCS: Small Molecule HER2 Inhibitor Tucatinib Improves Progression Free Survival in Patients with HER2-positive Metastatic Breast Cancer: in HER2CLIMB-05 Trial

Audio Medica News — Tue, 10 Feb 2026 15:28:01 +0000

Erika Hamilton MD; 2025 SABCS: Small Molecule HER2 Inhibitor Tucatinib Improves Progression Free Survival in Patients with HER2-positive Metastatic Breast Cancer: in HER2CLIMB-05 Trial

An interview with:

Erika Hamilton MD, Breast Cancer Research Program Leader, Department of Medical Oncology, Sarah Cannon Research Institute, Nashville, TN, USA.

SAN ANTONIO, USA—Adding the small-molecule tyrosine kinase inhibitor tucatinib to a combination of trastuzumab and pertuzumab as first-line maintenance therapy in patients with HER2-positive metastatic breast cancer improved progression-free survival and, according to research reported at the 2025San Antonio Breast Cancer Symposium, did not result in new safety signals.

After talking about the latest findings from the HER2CLIMB-05: phase three study at the conference, co-author Erika Hamilton from the Sarah Cannon Research Institute, Nashville USA, met up with Peter Goodwin from the Audio Journal of Oncology.

AUDIO JOURNAL OF ONCOLOGY: Erika Hamilton MD

IN: [GOODWIN]” I’m in San Antonio ….…..

OUT: ……of Oncology, I’m Peter Goodwin” 7:39

REFERENCE:

J Clin Oncol

2025 Dec 10:JCO2502600. doi: 10.1200/JCO-25-02600. Online ahead of print.

LINK:

TITLE:

HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination With Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer

AUTHORS:

Veronique Dieras 1, Giuseppe Curigliano 2 3, Miguel Martin 4, Florence Lerebours 5, Junji Tsurutani 6, Marie-France Savard 7, Katarzyna J Jerzak 8, Xichun Hu 9, Luciana Carla Martins de Aquino Pimentel 10, Ciara C O’Sullivan 11, Eriko Tokunaga 12, Alicia Okines 13 14, Chiun-Sheng Huang 15, William Jacot 16, Joohyuk Sohn 17, Eduardo Cronemberger Silva 18, Volkmar Mueller 19, Shan Yang 20, Giovanna Granata 21, Qi Shen 22, Libero Santarpia 23, Erika Hamilton 24;

HER2CLIMB-05 Investigators AFFILIATIONS:

1Medical Oncology Department, Centre Eugène Marquis, Rennes, France.

2European Institute of Oncology, IRCCS, Milano, Italy.

3Department of Oncology and Hemato-Oncology, University of Milano, Milano, Italy.

4Medical Oncology Service, Hospital General Universitario Gregorio Marañon, Universidad Complutense, CIBERONC, GEICAM, Madrid, Spain.

5Institut Curie, Saint-Cloud, Paris, France.

6The Innovative Center of Translational Research and Clinical Science for Cancer Therapy, Showa Medical University Hospital, Tokyo, Japan.

7Department of Medicine, The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada.

8Department of Medicine, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.

9Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

10Medical Oncology, Liga Norte-Rio Grandense Contra o Cancer, Natal, Brazil.

11Department of Medical Oncology, Mayo Clinic, Rochester, MN.

12Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.

13Medical Oncology, The Royal Marsden NHS Foundation Trust, London, United Kingdom.

14Institute of Cancer Research, London, United Kingdom.

15Breast Care Center, National Taiwan University Hospital, Taipei, Taiwan.

16Département d’Oncologie Médicale, Institut Regional du Cancer de Montpellier, Montpellier University, INSERM U1194, Montpellier, France.

17Division of Medical Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea.

18Medical Oncology, Centro Regional Integrado de Oncologia (CRIO), Fortaleza, Brazil.

19Department of Gynecology and University Breast Center, Universitaetsklinikum Hamburg-Eppendorf, Hamburg, Germany.

20Biostatistics, Pfizer Inc, Bothell, WA.

21Oncology Late Stage Development, Pfizer AG, Zug, Switzerland.

22Oncology, Research and Development, Pfizer Inc, Collegeville, PA.

23Oncology, Research and Development, Pfizer AG, Zug, Switzerland.

24Medical Oncology, Sarah Cannon Research Institute, Nashville, TN.

PMID: 41369677 DOI: 10.1200/JCO-25-02600

ABSTRACT:

Purpose:

The HER2CLIMB-05 study (ClinicalTrials.gov identifier: NCT05132582) is investigating the efficacy and safety of adding tucatinib to trastuzumab and pertuzumab as first-line (1L) maintenance therapy in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC).

Methods:

Patients with centrally confirmed HER2+ MBC without evidence of progression post induction therapy and no or asymptomatic brain metastases (BM) were enrolled. Patients were randomly assigned 1:1 to tucatinib (300 mg) or placebo twice a day combined with trastuzumab/pertuzumab. The primary end point is investigator-assessed progression-free survival (PFS); secondary end points include overall survival (OS), PFS per blinded independent central review, CNS-PFS, and safety.

Results:

Between March 2022 and July 2024, 654 patients were randomly assigned to tucatinib (n = 326) and placebo (n = 328) arms. All patients were female (median age, 54 years), 69.3% had de novo MBC, 52.6% were hormone receptor-positive, and 12.4% had presence/history of baseline BM. In this primary analysis, PFS was statistically significantly improved with addition of tucatinib versus placebo (hazard ratio, 0.641 [95% CI, 0.514 to 0.799]; P < .0001; median PFS: 24.9 v 16.3 months); a PFS benefit was seen regardless of the presence/absence of BM or hormone receptor status. OS data remain immature. The most common treatment-emergent adverse events (TEAEs) in the tucatinib arm were diarrhea (72.7%), nausea (33.1%), and elevated liver enzymes (ALT: 28.2%; AST: 25.8%), of which 6.1%, 0.9%, 13.5%, and 7.1%, respectively, were grade ≥3. In the tucatinib arm, 13.5% discontinued tucatinib because of TEAEs.

Conclusion:

Tucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC.

Wikipedia:

Tucatinib is a small molecule kinase inhibitor indicated in combination with trastuzumab and capecitabine for the treatment of adults with advanced unresectable or metastatic HER2-positive breast cancer, including those with brain metastases, who have received one or re prior anti-HER2-based regimens in the metastatic setting.[3]

Erika Hamilton SABCS AJ Oncology February 10, 2026

Wojciech Jurczak MD PhD; ASH 2025: Big Study Suggests Non-Covalent BTK Inhibitor Pirtobrutinib Could be New Standard-of-Care for Patients with Untreated Chronic Lymphocytic Leukemia

Audio Medica News — Thu, 05 Feb 2026 17:49:03 +0000

Wojciech Jurczak MD PhD; ASH 2025: Big Study Suggests Non-Covalent BTK Inhibitor Pirtobrutinib Could be New Standard-of-Care for Patients with Untreated Chronic Lymphocytic Leukemia

An interview with:

Wojciech Jurczak MD PhD, Professor of Hematology, National Research Institute of Oncology, Krakow, Poland

ORLANDO, USA— A non-covalent inhibitor of Bruton’s tyrosine kinase looks superior to the current standard of care as initial therapy for patients with chronic lymphocytic leukemia. That’s in research from Poland reported at the 2025 American Society of Hematology Annual Meeting in which the randomized CLL/SLL (BRUIN CLL-313; NCT05023980) phase three study compared pirtobrutinib with bendamustine plus rituximab in treatment-naïve patients.

Lead author Wojciech Jurczak MD PhD, Professor of Hematology at the National Research Institute of Oncology in Krakow, Poland, has been telling the Audio Journal of Oncology’s Peter Goodwin about the results:

AUDIO JOURNAL OF ONCOLOGY; Wojciech Jurczak MD PhD

IN: [GOODWIN] “Peter Goodwin…….

OUT: …….Peter Goodwin. 10:19

AMERICAN SOCIETY OF HEMATOLOGY ABSTRACT Number: LBA 3

Publication:

https://ashpublications.org/blood/article/146/Supplement%202/LBA-3/556927/Pirtobrutinib-vs-bendamustine-plus-rituximab-BR-in

STUDY TITLE:

Pirtobrutinib vs bendamustine plus rituximab (BR) in patients with CLL/SLL: First results from a randomized phase III study Examining a non-covalent BTK inhibitor in untreated patients

Blood (2025) 146 (Supplement 2): LBA-3.

https://doi.org/10.1182/blood-2025-LBA-3

AUTHORS:

Wojciech Jurczak, Michal Kwiatek, Jaroslaw Czyz, Ederson de Mattos, Ki-Seong Eom, Alexander Egle, Anna Panovská, Zhanet Grudeva-Popova, Hsuan-Jen Shih,

Luis Felipe Casado Montero, Paolo Sportoletti, Vu Minh Hua, James D’Olimpio,

Shinsuke Iida, Rodrigo Ito, Katherine Bao, Anne Fink, Weiji Su, Amy Ruppert Stark,

Alejandro Levy, Tomasz Wrobel

INSTITUTIONS:

1 National Research Institute of Oncology, Krakow, Poland,

2 AIDPORT Clinical Trials Hospital, Skorzewo, Poland,

3 Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Torun, Poland,

4 Hospital Amaral Carvalho Jau, São Paulo, Brazil,

5 Catholic Hematology Hospital, Seoul St. Mary’s Hospital, The

Catholic University of Korea, Seoul, Korea, Rep. of South,

6 Paracelsus University Hospital, Salzburg, Austria,

7 Masaryk University, Brno, Czech Republic,

8 Medical University of Plovdiv, Plovdiv, Bulgaria,

9 Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan,

10 HM CIOCC MADRID (Centro Integral Oncológico Clara Campal), Instituto de Investigación Sanitaria HM Hospitales, Madrid, Spain,

11 Institute of Hematology Centro di Ricerca Emato- Oncologica (CREO), University of Perugia, Perugia, Italy,

12 Liverpool Hospital, New South Wales, Australia,

13 Clinical Research Alliance, Westbury, United States,

14 Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan,

15 Eli Lilly and Company, Indianapolis, IN, United States,

16 Wroclaw Medical University, Wroclaw, Poland

Abstract

Introduction: Pirtobrutinib is a highly selective, non-covalent (nc) Bruton tyrosine kinase inhibitor (BTKi) that has demonstrated safety and efficacy in patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including pts previously treated with a cBTKi. While cBTKi have significantly improved progression-free survival (PFS) for untreated pts with CLL/SLL, there are no Phase 3 data assessing a ncBTKi specifically in the treatment-naïve setting, and significant improvements in overall survival (OS) are uncommon with monotherapy cBTKi. A recent head-to-head phase 3 trial (BRUIN CLL-314 presented at this meeting, ASH abstract 25-2587; NCT05254743) showed a favorable overall response rate (ORR) and a positive PFS trend with pirtobrutinib compared to the cBTKi ibrutinib in a subset of pts with treatment-naïve CLL. Here we present the first results from a randomized, open-label, global phase 3 trial specifically assessing the efficacy and safety of pirtobrutinib versus bendamustine plus rituximab (BR) in treatment-naïve pts with CLL/SLL (BRUIN CLL-313; NCT05023980).

Methods: Pts with previously untreated CLL/SLL, without del(17p), were randomized 1:1 to receive pirtobrutinib monotherapy (200 mg QD) or 6 cycles of BR, stratified by IGHV mutation status (mutated vs unmutated) and Rai stage (low/intermediate vs high). Pts with known CLL/SLL CNS involvement, Richter transformation, or significant cardiovascular disease were excluded. Responses were evaluated using iwCLL 2018 criteria. The primary endpoint was PFS assessed by independent review committee (IRC), and a stratified log-rank test compared IRC-assessed PFS between pirtobrutinib and BR using a 2-sided alpha level of 0.05. OS was a key secondary endpoint, gated on IRC-assessed PFS, with a small alpha of 0.000001 spent at this interim OS analysis. Other secondary endpoints included investigator (INV)-assessed PFS and safety. Efficacy analyses were based on the intent-to-treat population. Pts assigned to BR were eligible to cross over to receive pirtobrutinib if they had IRC-confirmed disease progression (PD), met study eligibility requirements, and needed therapy per iwCLL criteria. The data cutoff was 11 July 2025.

Results: 282 pts were randomized to receive either pirtobrutinib (n=141) or BR (n=141). At a median follow-up of 28.1 months, the primary endpoint of IRC-assessed PFS was significantly improved with pirtobrutinib compared with BR (HR: 0.199; 95% CI: 0.107, 0.367; p<0.0001). The 24-month PFS rate was 93.4% (95% CI: 87.6, 96.5) for pirtobrutinib and 70.7% (95% CI: 61.5, 78.1) for BR. IRC-assessed PFS benefit was consistently observed with pirtobrutinib among prespecified, clinically relevant patient subgroups, including patients with mutated IGHV (HR: 0.293, 95% CI: 0.094, 0.910), and unmutated IGHV (HR: 0.172, 95% CI: 0.083, 0.357). The PFS by INV was consistent (HR: 0.186; 95% CI: 0.093, 0.371; p<0.0001). The OS HR for pirtobrutinib versus BR was 0.257 (95% CI: 0.070, 0.934; p=0.0261), despite an effective crossover rate of 52.9% (18/34 pts with INV-assessed PD). The median treatment duration was 32.3 months for 140 pts receiving pirtobrutinib and 5.6 months for 132 pts receiving BR. The incidence of grade ≥3 TEAEs was 40.0% with pirtobrutinib and 67.4% with BR. Grade 5 TEAEs occurred in 1 pt receiving pirtobrutinib and 4 pts receiving BR, with none considered pirtobrutinib related and 1 (tumor lysis syndrome) considered BR related. Discontinuation of pirtobrutinib and BR due to TEAE occurred in 6 (4.3%) and 20 (15.2%) pts, respectively. Two pts (1.4%) receiving pirtobrutinib had a TEAE of atrial fibrillation/flutter, including only 1 of 20 pts aged ≥75 years.

Conclusions: In BRUIN CLL-313, pirtobrutinib significantly improved IRC-assessed PFS versus BR for pts with treatment-naïve CLL/SLL with one of the largest treatment effects ever observed for a single-agent BTKi against this comparator. Pirtobrutinib was well tolerated, consistent with its known safety profile, with low rates of discontinuation and atrial fibrillation/flutter. While OS data remained immature, a notable trend favoring pirtobrutinib was observed, despite 52.9% of BR pts crossing over to receive pirtobrutinib after PD. Taken together, these data suggest that pirtobrutinib may be considered a potential new standard-of-care treatment for pts with untreated CLL/SLL, including older pts who may receive only one line of therapy.

ASH PRESS RELEASE:

(ORLANDO, Dec. 9, 2025) – In a new trial, the Bruton tyrosine kinase (BTK) inhibitor pirtobrutinib increased the rate of survival without disease progression and was well tolerated with a more favorable safety profile when compared with bendamustine plus rituximab (BR) in patients with previously untreated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The data were presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition.

“We were able to prove that pirtobrutinib is an excellent drug both in terms of efficacy and tolerance,” said lead study author Wojciech Jurczak, MD, PhD, professor of hematology at the National Research Institute of Oncology in Kraków, Poland. “Our data show that it is not just overcoming resistance but is even more specific and selective than previous BTK inhibitors.”

Previous studies have shown pirtobrutinib, a first-generation non-covalent BTK inhibitor, to be efficacious against CLL/SLL that is relapsed or refractory after initial treatments. The current trial is the first to use pirtobrutinib in a first-line setting against a combination of bendamustine, a chemotherapy, and rituximab, a monoclonal antibody, which together constitute a common first-line combination treatment for CLL/SLL.

BTK inhibitors work by blocking the BTK enzyme, which plays a role in B cell growth and proliferation. Pirtobrutinib is developed to overcome the tendency for cancer cells to become resistant to previous-generation covalent BTK inhibitors.

CLL and SLL are slow-growing forms of non-Hodgkin lymphoma that develop when lymphocytes grow out of control and abnormal B cells build up in bone marrow (CLL) or lymph nodes (SLL). Each year, an estimated 4.5 out of every 100,000 adults are diagnosed with CLL or SLL.

The trial randomized 282 patients to receive a daily oral dose of pirtobrutinib continuously unless they developed unacceptable side effects, or six cycles of BR, administered via intravenous infusion every 28 days. At a median follow-up of 28 months, the rate of progression-free survival was significantly better with pirtobrutinib (93.4%) versus BR (70.7%), meeting the trial’s primary endpoint.

The progression-free survival trends were consistent across subgroups including among patients of different ages and among patients with or without Immunoglobin Heavy Chain Variable (IGHV) mutations, supporting pirtobrutinib as a new standard of care for first-line CLL/SLL treatment, said Dr. Jurczak. He noted that pirtobrutinib is more convenient for patients compared with covalent BTK inhibitors, some of which involve complex requirements around the timing of administration in relation to eating and drinking.

Overall survival will be formally assessed at a later date given the need for longer follow-up, but preliminary results favor pirtobrutinib for this secondary endpoint. Over half (52.9%) of patients in the BR arm who experienced disease progression crossed over to receive pirtobrutinib. From a statistical perspective, this amount of crossover would be expected to dilute any overall survival difference between study groups, so researchers noted that the trend toward improved overall survival is especially noteworthy.

Patients receiving pirtobrutinib experienced lower rates of adverse events, with 40.0% of patients in the pirtobrutinib arm experiencing treatment-related adverse events of grade 3 or higher compared with 67.4% in the BR arm. Treatment discontinuation due to adverse events was also less common in the pirtobrutinib arm (4.3%) compared with the BR arm (15.2%). The rate of atrial fibrillation or flutter in the pirtobrutinib arm was 1.4%, consistent with what would be expected among patients of a similar age in the general population.

Researchers said that the results suggest pirtobrutinib has strong potential as a first-line treatment for CLL/SLL. However, the study used a continuous administration strategy and was also limited by pirtobrutinib’s interactions with antibiotics and antifungals. To pave the way for practical adoption of pirtobrutinib as first-line treatment, Dr. Jurczak suggested that additional work is needed to develop a fixed-duration regimen for the drug and to determine which agents are best to use after pirtobrutinib if the cancer returns. He also noted that pirtobrutinib should be paused if patients develop infections during treatment, given the drug’s interaction with antibiotics and antifungals.

Additional studies are underway to assess a lower dosing strategy for pirtobrutinib and move toward fixed-duration rather than continuous administration.

This study was funded by Lilly, maker of pirtobrutinib.

Wojciech Jurczak ASH 2025

Gaorav Gupta MD PhD; SABCS 2025: Pre-Op Radiation Improved T-cell Infiltration in Hormone Receptor-positive, HER2-negative Invasive Breast Cancer; Could Boost Systemic Therapy Responses

Audio Medica News — Tue, 03 Feb 2026 15:19:24 +0000

Gaorav Gupta MD PhD; SABCS 2025: Pre-Op Radiation Improved T-cell Infiltration in Hormone Receptor-positive, HER2-negative Invasive Breast Cancer; Could Boost Systemic Therapy Responses

An interview with:

Gaorav Gupta MD PhD, Associate Professor Radiation Oncology, University of North Carolina at Chapel Hill, North Carolina, USA

SAN ANTONIO, USA—Patients with the most common form of breast cancer could respond better to immunotherapy and chemotherapy if they received neo-adjuvant radiation therapy. This is the implication of findings from the TBCRC-053 (P-RAD) study in patients with hormone receptor-positive, HER2-negative breast cancer which found an increase of T-cell infiltration among patients who had pre-operative radiation compared with those who did not.

The study findings were reported at the 2025 San Antonio Breast Cancer Symposium by Garav Gupta, MD PhD, an Associate Professor at the University of North Carolina at Chapel Hill, USA. After his talk at the conference he met up with the Audio Journal of Oncology’s Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Garav Gupta MD PhD

IN: [GOODWIN] “I’m at the San Antonio….

OUT: ……and the Audio Journal of Oncology, Goodbye” 8:58

SABCS 2025 Presentation Number: GS2-05.

TITLE:

Primary Results from the HR+/HER2- Cohort of TBCRC-053 (P-RAD): A Randomized Trial of No, Low, or High Dose Preoperative RADiation with Pembrolizumab and Chemotherapy in Node-Positive, HER2-Negative Breast Cancer

Authors

Gupta1, A. Y. Ho2, F. Gharibpoor3, Y. Abdou3, J. D. Anampa4, R. C. Blitzblau2, B. C. Calhoun5, D. L. Casey3, S. F. Dent6, L. A. Carey7, J. R. Bellon8, L. E. Warren8, J. Lu9, T. J. Hieken10, A. G. Taghian11, A. Bardia12, T. Traina13, G. Plitas14, K. Gallagher15, K. Daugherty16, A. Thompson17, I. Krop18, A. Wolff19, E. Mittendorf20, J. Fox21, H. Garber22, E. Hwang23, A. J. Khan24, J. P. Loene25, R. Mutter26, S. Patil27, C. Santa-Maria19, B. V. Vincent7, J. L. Wright3, L. Spring28; 1Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 2Radiation Oncology, Duke University, Durham, NC, 3Radiation Oncology, University of North Carolina, Chapel Hill, NC, 4Medical Oncology, Albert Einstein College of Medicine, Bronx, NY, 5Pathology, University of North Carolina, Chapel Hill, NC, 6Medical Oncology, University of Rochester, Rochester, NY, 7Medical Oncology, University of North Carolina, Chapel Hill, NC, 8Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, 9Medical Oncology, Montefiore Medical Center, Bronx, NY, 10Surgery, Mayo Clinic, Rochester, MN, 11Radiation Oncology, Massachusetts General Hospital, Boston, MA, 12Medical Oncology, University of California Los Angeles, Santa Monica, CA, 13Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 14Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 15Surgery, University of North Carolina, Chapel Hill, NC, 16Cancer Center Protocol Office, Massachusetts General Hospital, Boston, MA, 17Surgery, Baylor College of Medicine, Houston, TX, 18Medical Oncology, Yale School of Medicine, New Haven, CT, 19Medical Oncology, Johns Hopkins University, Baltimore, MD, 20Surgery, Dana-Farber Cancer Institute, Boston, MA, 21Radiation Oncology, Montefiore Medical Center, Bronx, NY, 22Medical Oncology, MD Anderson Cancer Center, Houston, TX, 23Surgery, Duke University, Durham, NC, 24Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 25Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 26Radiation Oncology, Mayo Clinic, Rochester, MN, 27Biostatistics, Cleveland Clinic, Cleveland, OH, 28Medical Oncology, Massachusetts General Hospital, Boston, MA.

Abstract

Introduction: Hormone receptor positive (HR+), HER2- breast cancer (BC) is the most common subtype of BC. Despite advances in chemotherapy and endocrine therapy optimization, local and systemic recurrences frequently occur, especially for patients with node-positive disease. Recent data suggest a subset of patients with this tumor phenotype may benefit from the addition of anti-Programmed Death-1(aPD1) to neoadjuvant chemotherapy. However, T-cell infiltration (TCI), a biomarker of response to a PD1 and chemotherapy, is typically low in this BC subtype. Preclinical models show that combining preoperative radiation therapy (preop RT) with immune checkpoint inhibitors can enhance TCI and anti-tumor immunity. We conducted the first randomized trial to test whether no-, low- or high-dose RT combined with aPD1 increases TCI and improves responses in non-irradiated, metastatic lymph nodes in HR+/HER2- BC (NCT04443348).

Materials & Methods: Eligible patients had ER and/or PR≥10%, HER2 negative invasive BC with clipped and biopsy-proven positive axillary node(s), cT1c-T4c, cN1-3, and at least one of the following criteria: grade 3 or grade 1-2 with cN2-N3, Ki67 >20%, or high genomic assay score. Between 2022-2024, 51 patients from 10 centers were randomized to no (0Gy; control arm), low (9Gy) or high (24Gy) doses of preop RT to the primary tumor with concurrent pembrolizumab followed by a 2-week tumor biopsy. Stratification factors were T1c vs. T2-4 and N1 vs. N2-3. Patients subsequently received pembrolizumab with 12 weeks of paclitaxel, followed by 4 cycles of adriamycin-cyclophosphamide (q2wk or q3wk) with pembrolizumab (200 mg q3 wks or 400 mg q6 wks). Surgery and adjuvant therapy followed standard-of-care. Dual co-primary endpoints were 2wk tumor TCI and nodal pathologic complete response (ypN0) at time of definitive surgery. TCI was assessed by multiplex immunofluorescence (pan-cytokeratin, CD3, CD8), using a rank-based Immunoscore (range 0-1), compared to baseline reference biopsies via two-tailed Mann-Whitney test. ypN0 was evaluated non-comparatively. Secondary endpoints included pCR and Residual Cancer Burden (RCB) 0/1.

Results: Among 51 patients enrolled, 49 were evaluable for TCI and 48 for the ypN0 endpoint. Median age was 49.5 years (range 23-78). The cohort had a high-risk clinical profile: 92% had cT2-4, 50% N2-3, and 62% grade 3 tumors. Median ER and PR positivity were 90% (20-100) and 68% (1-98), respectively. Multifocal or multicentric tumors were present in 32%. TCI was assessed at 2 weeks post-treatment. The proportion of tumors with TCI in the upper quartile increased with RT dose escalation: 31% (0Gy), 40% (9Gy), and 53% (24Gy). Median TCI scores at 2 weeks were 0.60 (0Gy), 0.56 (9Gy), and 0.82 (24Gy), compared to a median baseline value of 0.50 from untreated reference samples. A statistically significant increase in TCI was observed only in the 24Gy cohort relative to the untreated group (p=0.027). 70.8% underwent mastectomy, with 39.6% receiving immediate reconstruction. 8% experienced G2/3 wound complications, balanced across arms. Median number of lymph nodes removed was 6.5 (1-42). The overall ypN0 rate was 29%, and 24%(0Gy), 29%(9Gy) and 33%(24Gy) per arm. pCR/RCB 0-1 rates were 18%/27% in the entire cohort and 6%/18%(0Gy), 29%/29%(9Gy), and 19%/33%(24Gy), respectively.

Conclusion: The addition of 24Gy preop RT to a PD1 significantly increased tumor TCI in HR+/HER2- early-stage BC. Non-irradiated nodal response rates were promising despite over one-third of the study population with grade 1/2 tumors and high disease burden, laying the foundation for a future randomized trial comparing the efficacy of this novel approach against standard of care for node-positive HR+/HER2- BC.

Gaorav Gupta MD PhD, AJ Oncology from SABCS 2025

February 3, 2026https://www.audiomedica.com/wp-content/2026/02/Gaorav-Gupta-SABCS-2025-PRODUCTION-MASTER.mp3

Lorenzo Falchi MD; ASH 2025: Bispecific Antibody Epcoritamab Combination Beats Standard of Care for Patients with Relapsed/Refractory Follicular Lymphoma

Audio Medica News — Fri, 30 Jan 2026 23:56:45 +0000

Bispecific Antibody Epcoritamab Combination Beats Standard of Care for Patients with Relapsed/Refractory Follicular Lymphoma

An interview with:

Lorenzo Falchi MD, Lymphoma Service, Attending Physician, Memorial Sloan Kettering Cancer Center, New York NY, USA

ORLANDO, USA—A bispecific antibody to treat follicular lymphoma has outperformed standard rituximab plus lenalidomide in patients whose disease has relapsed or who are refractory to standard first-line treatments. This was in the phase three epcore FL-1 trial in which patients receiving rituximab and lenalidomide were randomly assigned to have the CD3xCD20 bispecific Epcoritamab or a placebo added to their therapy.

At the 2025 Annual Meeting of the American Society of Hematology the findings were reported by Lorenzo Falchi MD, Lymphoma Service, Attending Physician, Memorial Sloan Kettering Cancer Center, New York NY, USA, who afterwards spoke with the Audio Journal of Oncology’s Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Lorenzo Falchi MD

IN: [GOODWIN] “ I’m at the American …..

OUT: ……..of Oncology, I’m Peter Goodwin 7:58

ASH 2025 ABSTRACT TITLE:

“primary Phase 3 results from the epcore FL-1 trial of epcoritamab with rituximab and lenalidomide (R2) versus R2 for relapsed or refractory follicular lymphoma”

https://ashpublications.org/blood/article/146/Supplement%201/466/554305/primary-Phase-3-results-from-the-epcore-FL-1-trial

Blood (2025) 146 (Supplement 1): 466.

https://doi.org/10.1182/blood-2025-466

AUTHORS

Lorenzo Falchi1, Marcel Nijland2, Huiqiang Huang3, Kim Linton4, John Seymour5, Rong Tao6, Michal Kwiatek7, Abel Costa8, Theodoros Vassilakopoulos9, Richard Greil10, Ana Jiménez Ubieto 11, ShaneGangatharan12, Ohad Benjamini13, Catherine Thieblemont14, Alessandra Tucci15, Anna ElinderCamburn16, Arpad Illes17, Jan Novak18, Miguel Pavlovsky19, Andrew McDonald20, Dok Hyun Yoon21, Yuko Mishima22, Gauri Sunkersett23, Jian Mei23, Nabanita Mukherjee23, Feng Zhu23, Elena Favaro24, Franck Morschhauser25

INSTITUTIONS:

1 Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, United States,

2 University Medical Center Groningen, University of Groningen, Groningen, Netherlands,

3 Sun Yat-sen University, Guangzhou, China,

4 The Christie NHS Foundation Trust, Manchester Cancer Research Centre, and Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom,

5 Peter MacCallumCancer Centre and The Royal Melbourne Hospital, Melbourne, Australia,

6 Fudan University Cancer Hospital, Shanghai, China,

7 Aidport Clinical Trials Hospital, Skorzewo, Poland,

8Instituto D’Or de Pesquisa e Ensino, São Paulo, Brazil,

9 Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece,

10 Paracelsus Medical University Salzburg; Salzburg Cancer Research InstituteCenter for Clinical Cancer and Immunology Trials; Cancer Cluster Salzburg, Salzburg, Austria,

11 Hospital Universitario 12 de Octubre, Madrid, Spain,

12 Fiona Stanley Hospital, Murdoch, Australia,

13 The Chaim Sheba Medical Center, Ramat Gan, Israel,

14 Hôpital Saint-Louis, Paris, France,

15 ASST degli Spedali Civili di Brescia, Brescia, Italy,

16 North Shore Hospital, Auckland, New Zealand,

17 Debreceni Egyetem-Klinikai Kozpont, Debrecen, Hungary,

18 Fakultni nemocnice Kralovske Vinohrady, Prague, Czech Republic,

19 FUNDALEU, Buenos Aires, Argentina,

20 Alberts Cellular Therapy, Gauteng, South Africa,

21 Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea, Rep. of South,

22 Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan,

23 AbbVie Inc., North Chicago, IL, United States,

24 Genmab, Copenhagen, Denmark,

25 Hôpital Claude Huriez, Lille, France

INTRODUCTION:

Patients (pts) with relapsed/refractory (R/R) follicular lymphoma FL have limited second line (2L) treatment options, rituximab and lenalidomideR2being the only 2L alternative to immunochemotherapy-based therapy. Epcoritamab (epcor), a CD3xCD20 bispecific antibody, is approved for R/R FL as monotherapy after ≥2 lines of systemic therapy. Epcor plus R2 (E+R2) is a chemotherapy-free regimen which showed promising antitumor activity (97% overall response rate [ORR], 87% complete response [CR] rate) and manageable safety in the phase 1b/2 EPCORE NHL-2 trial (Falchi et al, ASH 2024). We report the results of EPCORE FL-1: the first global phase 3 trial of fixed-duration bispecific antibody regimen E+R2 vs R2 in pts with 2L+ FL (NCT05409066).

METHODS:

Adults with CD20+ FL R/R after at least 1 prior line, who met GELF criteria, were randomized to receive E+R2or R2for up to 12 cycles (C). Subcutaneous epcor was administered using a 2-step-up dose (2SUD) or 3-step-up dose (3SUD) regimen and full doses (48mg) thereafter. Epcor was administered weekly in C1–3 and q28 days from C4–12. Intravenous rituximab was administered weekly in C1 and q28 days during C2–5. Oral lenalidomide was administered daily from day 1–21 during C1–12. Pts received mandatory CRS prophylaxis in C1. Dual primary endpoints were ORR and progression-free survival (PFS) assessed by independent review committee per Lugano criteria. Secondary endpoints included CR rate (CRR), overall survival (OS), duration of response/CR (DOR/DOCR), and safety.

RESULTS:

As of the Jan 10, 2025 data cut-off, 488 pts were randomized to receive E+R2 (N=243) or R2alone (N=245). Pt characteristics were generally well balanced across the two arms. Pts treated with E+R2 vs R2had a median age of 60 years (range, 30–84) vs 63 years (range, 24–89), Ann Arbor stage III-IV in 84.8% vs 81.6%, double refractory disease in 35.4% vs 35.9%, and POD24 in 43% vs 36%, respectively. The median number of prior lines of treatment was 1 (range, 1–7) vs 1 (range, 1–6), respectively. The median duration of follow-up was 10.4 months (95% CI: 9.8, 11.1). A preplanned interim analysis was conducted after the first 232 pts achieved 12 months of follow-up post-randomization, and the ORR was significantly improved in pts treated with E+R2 (95.7% [95% CI: 90.2, 98.6]) vs R2(81.0% [95% CI: 72.7, 87.7]; P<.0001). The 12-month DOR was 91.4% (95% CI: 84.0, 95.4) vs 57.0% (95% CI: 44.2, 68.0), respectively. In the full ITT population (N=488), PFS was significantly longer in pts treated with E+R2 vs those treated with R2 (hazard ratio [HR] 0.21; 95% CI: 0.13, 0.33; P<.0001). Additionally, E+R2 led to a significant improvement in CRR vs R2 (74.5% [95% CI: 68.5, 79.8] vs 43.3% [95% CI: 37.0, 49.7]; P<.0001). Similar improvements in response rates were observed in all pre-definedhigh-risksubgroups (eg, primary/double refractory disease, POD24). Among 131 pts receiving 3SUD in the E+R2arm, CRS events were low grade (G) and occurred in 24.4% of pts (G1, 19.1%; G2, 5.3%); most occurred at time of first 48mg full epcor dose and all resolved. One event of ICANS (G1) was reported in the E+R2 arm and resolved. G3/4 TEAEs were reported in 88.1% of pts receiving E+R2vs 62.2% with R2, the difference being primarily driven by higher rates of G3/4 neutropenia (66.3% vs 37.8%) and G3/4 infections (29.2% vs 13.4%). Rates of G3/4 febrile neutropenia were 6.2% (E+R2) vs 2.1% (R2). Fatal TEAEs occurred in 0.8% (n=2) vs 2.9% (n=7) with E+R2 vs R2, respectively; with no fatal events deemed related to epcor. TEAEs leading to discontinuation occurred in 16.0% of cases for E+R2 vs 11.8% for R2. Updated data from prespecified second interim analysis on all efficacy endpoints will be available at the time of presentation.

CONCLUSION:

Epcor is the first CD20xCD3 bispecific antibody to demonstrate clinical benefit over standard of care in a randomized phase 3 trial in patients with FL, with statistically significant improvements in ORR, CR rate, and a 79% reduction in the risk of progression or death. Higher rates of G3/4 neutropenia and infections were observed in E+R2, but these were manageable and none were fatal. CRS was low grade and the timing was predictable. E+R² sets a new benchmark as a readily available treatment, is suitable for outpatient administration, and has the potential to become a new standard of care in 2L+ FL.

260130 Audio Journal of Oncology ASH 2025

Christian F. Singer MD; 2025 SABCS: Denosumab Bone Protection in ER-Positive Early Breast Cancer Brings Added Benefit with Progesterone Receptor Positive Tumors: ABCSG 18 Study Findings

Audio Medica News — Thu, 29 Jan 2026 15:05:51 +0000

Denosumab Bone Protection in ER-Positive Early Breast Cancer Brings Added Benefit with Progesterone Receptor Positive Tumors: ABCSG 18 Study Findings

An interview with:

Christian F Singer MD, Professor of Clinical-Translational Gynecological Oncology, Medical University of Vienna, Austria

SAN ANTONIO, USA—Post-menopausal women treated with denosumab to give bone protection along with their aromatase inhibitor hormone therapy did better if their tumors tested positive for the progesterone receptor as well as for the estrogen receptor. This is according to finding from the ABCSG 18 Study (of the Austrian Breast and Colorectal Cancer Study Group).

The research was reported at the 2025 San Antonio Breast Cancer Symposium by Christian Singer MD, Professor of Clinical-Translational Gynecological Oncology at the Medical University of Vienna, Austria. The Audio Journal of Oncology’s Peter Goodwin called to see him at his poster to find out more:

AUDIO JOURNAL OF ONCOLOGY: Christian F. Singer MD

IN: [GOODWIN] “We are at the San Antonio ..…..

OUT ……..Journal of Oncology, I’m Peter Goodwin. 7:22secs

ABSTRACT:

Authors:

Singer1, D. Hlauschek2, D. Egle3, A. Reiner4, G. G. Steger5, G. Huber6, R. Greil7, G. Rinnerthaler8, F. Fitzal9, C. Brunner3, C. Suppan8, G. Pfeiler1, S. P. Gampenrieder7, M. Seifert1, S. Kacerovsky-Strobl10, C. Deutschmann1, K. Wimmer11, M. Balic12, R. Jakesz5, C. Fesl2, H. Fohler13, M. Gnant5;

Institutions:

1Department of Gynecology and Obstetrics, Medical University of Vienna, Vienna, AUSTRIA, 2Statistics Department, Austrian Breast and Colorectal Cancer Study Group (ABCSG), Vienna, AUSTRIA, 3Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, AUSTRIA, 4Institut für Klinische Pathologie, Molekularpathologie und Mikrobiologie, Klinik Donaustadt, Vienna, AUSTRIA, 5Comprehensive Cancer Center, Medical University of Vienna, Vienna, AUSTRIA, 6Ordination Dr. Huber, Breast Center Carinthia, St. Veit/Glan, AUSTRIA, 7Department of Internal Medicine III, Oncologic Center, Salzburg Cancer Research Institute, Paracelsus Medical University, Salzburg, AUSTRIA, 8Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, AUSTRIA, 9Department of Surgery and Breast Health Center, Hanusch Hospital, Vienna, AUSTRIA, 10Department of Surgery, Klinikum Donaustadt, Vienna, AUSTRIA, 11Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna, AUSTRIA, 12Division of Oncology, University of Pittsburgh Medical School, Hillmans Cancer Center, Pittburgh, PA, 13Management, Austrian Breast and Colorectal Cancer Study Group (ABCSG), Vienna, AUSTRIA.

Title:

The improved long-term outcome in denosumab-treated postmenopausal women with early luminal breast cancer in ABCSG 18 is driven by progesterone receptor (PR)-positive tumors.

Background:

The biological effects of progesterone are mediated through the RANK/RANK-ligand system, which promotes tumor growth and malignant behavior in breast cancer models. In the large prospective, double-blind, placebo-controlled, phase 3 ABCSG 18 trial we have demonstrated that the addition of the RANK ligand denosumab dramatically reduces fractures compared to placebo, but also improves disease-free survival (DFS), and overall survival (OS) in aromatase inhibitor-treated postmenopausal patients with early luminal breast cancer.

Patients and Methods:

Tumor histological grade, as well as immunohistochemically quantified Ki-67, estrogen receptor (ER), and progesterone receptor (PR) data were collected from 2,026 patients. ER and PR were assessed according to the Allred score and considered positive if ≥3. Disease-free survival (DFS), distant recurrence-free (DRFS), and overall survival (OS) data were prospectively collected during a median follow-up (FU) of 8.1 years as part of the ABCSG 18 study. Cox Models were used to evaluate the association with outcome.

Results:

Overall, luminal A-like tumors had a better DFS, DRFS, and OS than luminal B-like tumors, but PR expression per se was not prognostic in this large prospective clinical trial. Patients with PR positive tumors, however, who were treated with denosumab, enjoyed a considerably better long-term outcome than patients who had been randomized to the placebo arm (HR for DFS: 0.80; 95% CI 0.65-0.98; HR for DRFS: 0.68; 95% CI 0.51-0.90; HR for OS 0.63; 95% CI 0.46-0.88). In contrast, in patients with PR-negative tumors, no differences in long-term outcomes between the denosumab or placebo arm of the trial were observed (HR for DFS: 0.87; 95% CI 0.46-1.64; HR for DRFS: 1.19; 95% CI 0.53-2.66; HR for OS 0.99; 95% CI 0.37-2.65). While the HR for DFS in denosumab vs placebo patients remained stable with increasing Allred scores, HRs for DRFS and OS improved with increasing Allred scores, thereby suggesting that the efficacy of denosumab depends on the degree of intra-tumoral PR expression.

Conclusion:

Our results indicate that the long-term outcome benefit for adjuvant denosumab in this large prospective randomized placebo-controlled trial is driven by patients with PR-positive tumors. The disruption of PR signaling, either via PR antagonization or by RANKL inhibition, could therefore be a promising therapeutic strategy in luminal breast cancer.

260119 Christian F. Singer MD A J Oncology

From:

SABCS 2025 Wednesday Dec. 10 Poster 5:00 pm

Amir Fathi MD; ASH 2025: Paradigm Study Finds Young, Fit Adults with Acute Myeloid Leukemia Do Better with Gentler Azacitidine/Venetoclax Initial Therapy

Audio Medica News — Wed, 28 Jan 2026 11:34:58 +0000

Amir Fathi MD; ASH 2025: Paradigm Study Finds Young, Fit Adults with Acute Myeloid Leukemia Do Better with Gentler Azacitidine/Venetoclax Initial Therapy

An interview with:

Amir Fathi MD, Leukemia Program Director, Massachusetts General Hospital and Associate Professor of Medicine, Harvard Medical School, Boston, USA.

ORLANDO, USA— Young, fit adults with acute myeloid leukemia had fewer toxicities and better response rates when treated with a combination of venetoclax plus azacytidine in comparison with similar group of patients who had standard induction chemotherapy. This was in the Paradigm phase two multi center randomized study reported at the 2025 Annual Meeting of the American Society of Hematology by Amir Fathi MD, the Leukemia Program Director at the Massachusetts General Hospital in Boston and Associate Professor of Medicine at Harvard Medical School, Boston, USA. At the conference he met up with Audio Journal of Oncology reporter Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Amir Fathi MD

IN: [GOODWIN] “Peter Goodwin here at the American Society …..

OUT: ………of Oncology, I’m Peter Goodwin.” 10:01 secs

LINK:

https://ashpublications.org/blood/article/146/Supplement%201/6/553639/Results-from-paradigm-a-phase-2-randomized-multi

American Society of Hematology 2025 Annual Meeting

ABSTRACT 6

Results from paradigm – a phase 2 randomized multi-center study comparing azacitidine and venetoclax to conventional induction chemotherapy for newly diagnosed fit adults with acute myeloid leukemia

AUTHORS:

Amir Fathi, Alexander Perl, Geoffrey Fell, Brian Jonas, Brittany Ragon, Alice Mims, Uma Borate, Gabriel Mannis, Karen Quillen, Max Stahl, Paul Koller, Andrew Artz, Monzr M. Al Malki, Guido Marcucci, Mary Linton Peters, Timothy Graubert, Peter Westervelt, Philip Amrein, Hanno Hock, Andrew Brunner, Gabriela Hobbs, Rupa Narayan, Michelle Lee, Brandon Aubrey, Alyssa Watson, Richard Hao, Shilton Dhaver, Michael Grunwald, Yi-Bin Chen, Andrew Matthews, Christopher Hourigan, Brent Wood, Donna Neuberg, Areej El-Jawahri, Ibrahim Aldoss

INSTITUTIONS:

1 Massachusetts General Hospital / Harvard Medical School, Boston, MA, United States, 2 Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, United States, 3 Dana Farber Cancer Institute, Boston, MA, United States, 4 University of California Davis Comprehensive Cancer Center, Sacramento, CA, United States, 5 Levine Cancer Institute, Atrium Health, Charlotte, NC, United States, 6 The Ohio State University, Columbus, OH, United States, 7 Stanford University School of Medicine, Stanford, CA, United States, 8 Beth Israel Deaconess Medical Center, Boston, MA, United States, 9 Yale School of Medicine, New Haven, CT, United States, 10 City of Hope, Duarte, CA, United States, 11 Massachusetts General Hospital, Boston, MA, United States, 12 MaineHealth, Brunswick, ME, United States, 13 Fralin biomedical research institute, Virgina Tech University, Roanoke, VA, United States, 14 Children’s Hospital Los Angeles, University of Southern California, Los Angeles, MA, United States

Introduction:

For decades, standard upfront treatment for acute myeloid leukemia (AML) among fit patients (pts) has been intensive induction chemotherapy (IC), typically with cytarabine and anthracyclines. However, long-term outcomes remain poor, and IC continues to pose substantial short- and long-term morbidities, with significant burden to pts and hospitals. VIALE-A, a phase 3 trial of IC-ineligible pts, established superiority of azacitidine and venetoclax (aza-ven) vs aza alone, with a median OS of 15 months and composite remission rate (CCR) of 66%, which compare favorably to that expected for IC among older pts. We prospectively tested whether aza-ven was superior to IC in fit pts and could challenge the current treatment standard.

Methods:

This open-label, multicenter, phase II randomized clinical trial compared the therapeutic activity of conventional IC (7+3 regimen or liposomal daunorubicin and cytarabine [CPX351]) to aza-ven among IC-eligible pts aged ≥ 18. Pts with core binding factor fusions, FLT3 mutations, or NPM1 mutations (unless aged ≥ 60) were excluded. The IC arm incorporated cycles of chemotherapy consolidation following induction, for use as clinically appropriate per current standard of care. Pts were allowed to proceed to transplant (HCT) on both arms following response on protocol-directed therapy.

The primary endpoint was event free survival (EFS), with events defined as progressive disease, persistent disease prompting therapy change, relapse, hospice, or death. Among secondary endpoints were response rates, OS, toxicity, measurable residual disease (MRD), hospitalization metrics, and quality of life (QOL). Pts were stratified by age (≥ 65 vs < 65) and pre-randomization selection in the IC arm to 7+3 or CPX351. EFS is estimated by Kaplan Meier method and assessed by log rank test and Cox PH regression. Clinical responses are assessed using an exact binomial test. Significance is declared at the two-sided 0.1 type I error.

Results:

As of 7/25/2025, 172 pts at 9 US centers were randomized to aza-ven (n=86) or IC (n=86), and accrual is complete. Median age was 64 for aza-ven and 65 for IC pts. 55% and 60% were male in the aza-ven and IC arms, respectively, and 65% and 69% were White. The majority of pts were ELN 2022 adverse risk (72%), 15% were intermediate-, and 12% favorable-risk. Distribution of risk categories did not differ across arms (p=0.44), nor did the proportions of TP53, NPM1, or IDH1/2 mutations. Median number of cycles completed were 4 for aza-ven and 2 for IC pts. Among IC pts, 54% received 7+3, and the rest, CPX351.

By intent to treat analysis, the rate of overall response (OR=CR+CRh+CRi+PR+MLFS) was significantly higher in the aza-ven arm (88% vs 62%; P<0.001), as was CCR (CR+CRh+CRi) (81% vs 55%; P<0.001). CR rates for aza-ven and IC were not significantly different (59% vs 50%; P=.066). Procession to HCT following response from protocol therapy differed across arms (P=0.009) – 52 (61%) pts on aza-ven and 34 (40%) on IC arms. With a median follow-up of 16 months, 1-year EFS was 53% for aza-ven and 39% for the IC arm. EFS overall was significantly superior in the aza-ven arm (HR 0.61; P=0.017). There was no significant age effect on EFS when included with treatment in the Cox PH model, and HR for treatment remained significant (0.61; P=0.018).

Grade (G)3/4 therapy-related adverse events in ≥10% were mainly hematologic and at similar rates across arms. G3/4 lung infections and sepsis occurred in 12% and 7% of aza-ven, and 15% and 11% of IC pts. 30- and 60-day mortality on the aza-ven arm were both 0%, vs 3.5% and 4.7% in the IC arm, respectively.

At 2 weeks, aza-ven pts reported significantly better QOL (P=0.001), symptom burden (P=0.019), and depression symptom (P=0.007) scores, vs IC. Aza-ven pts were less likely to need ICU care (0 vs 9.8%; P=0.003), and experienced fewer inpatient days for the index hospitalization (15 vs 36; P<0.001) and during the first 6 months (41 vs 58; P<0.001).

Conclusion:

The study has met its primary endpoint. Aza-ven was associated with significantly improved EFS, as well as higher rates of OR and CCR, vs IC in younger, IC-eligible pts. Overall survival data continue to mature. A greater proportion of pts successfully went to HCT following response to aza-ven than those to IC. Aza-ven led to numerically fewer serious infectious complications, significantly improved QOL and symptom burden during initial therapy, with less time in the hospital and the ICU.

Keywords:

Drug Development, Adverse Events , Research, Treatment Considerations, Myeloid

Malignancies, Measurable Residual Disease , Clinical Trials, Diseases, Study Population, Clinical Research, Human

Jennifer A. Woyach MD, ASH 2024: The Non-Covalent Bruton’s Tyrosine Kinase-Inhibitor Pirtobrutinib is As Effective, While Less Toxic, In Relapsed/Refractory Chronic Lymphocytic Leukemia

Audio Medica News — Sat, 24 Jan 2026 00:12:44 +0000

Jennifer A. Woyach MD, ASH 2024: The Non-Covalent Bruton’s Tyrosine Kinase-Inhibitor Pirtobrutinib is As Effective, While Less Toxic, In Relapsed/Refractory Chronic Lymphocytic Leukemia

An interview with:

Jennifer A. Woyach MD, Director of Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States

ORLANDO, USA—The possibility of using a less toxic Bruton’s tyrosine kinase (BTK) inhibitor to treat chronic lymphocytic leukemia/small lymphocytic lymphoma—especially in treatment naïve patients— could become a reality according to promising findings from the first randomized phase III study comparing a non-covalent with a covalent BTK inhibitor. Study findings were announced at the American Society of Hematology 2025 Annual Meeting by Jennifer A. Woyach MD, Director of the Division of Hematology at the Ohio State University Comprehensive Cancer Center in Columbus, USA. After her talk at the conference Dr. Woyach discussed the data with the Audio Journal of Oncology’s Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Jennifer Woyach MD

IN: [GOODWIN]“Peter Goodwin here in Orlando Florida ….

OUT: ….in Orlando Florida, I’m Peter Goodwin. 5:39 secs

PUBLICATION REFERENCE:

https://ashpublications.org/blood/article/146/Supplement%201/683/551183/Pirtobrutinib-vs-ibrutinib-in-treatment-naive-and

Blood (2025) 146 (Supplement 1): 683.

https://doi.org/10.1182/blood-2025-683

TITLE:

Pirtobrutinib vs ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL: Results from the first randomized phase III study comparing a non-covalent and covalent BTK inhibitor

Jennifer Woyach, Lugui Qiu, Sebastian Grosicki, Tomasz Wrobel, Marcelo Capra, Jaroslaw Czyz, Shuhua Yi, Ki-Seong Eom, Anna Panovská, Wojciech Jurczak, Kamel Laribi, Lutz Jacobasch, Ross Baker, Richy Agajanian, Alejandro Berkovits, Muhit Özcan, Stephane Lepretre, Catherine Coombs, Paula Cramer, Katharine Lewis, Marisa Hill, Katherine Bao, Yuanyuan Bian, Amy Ruppert Stark, Ching Ching Leow, William Wierda

2025 ASH Orlando, Abstract: 683

Abstract Title :

Pirtobrutinib vs ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL: Results from the first randomized phase III study comparing a non-covalent and covalent BTK inhibitor

Category: 600s – Hematologic Malignancy

Review Category: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological

Lead Author:

Jennifer A. Woyach MD, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States

Institutions:

1 The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States,

2 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology& Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China,

3 Medical University of Silesia, Department of Cancer Prevention, Katowice, Poland,

4 Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Medical University of Wroclaw, Wroclaw, Poland,

5 Centro Integrado de Hematologia e Oncologia, Hospital Mãe de Deus, Porto Alegre, Brazil, 6 Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Departament of Hematology, Bydgoszcz, Torun, Poland,

7 Department of Hematology, Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, Rep. of South,

8 Department of Internal Medicine -Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic,

9 Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland,

10 Department of Hematology, Centre Hospitalier Le Mans, Le Mans, France,

11 Praxis of Haematology and Oncology, Dresden, Germany,

12 Western Australia Centre for Thrombosis and Haemostasis, Perth Blood Institute,

Murdoch University, Perth, Australia,

13 The Oncology Institute of Hope and Innovation, Whittier, CA, United States,

14 Inmunocel, Santiago, Chile, 15 Ankara University, School of Medicine, Ankara, Türkiye, 16 Centre de Lutte Contre le Cancer – Centre Henri Becquerel, Rouen, France,

17 University of California Irvine, Irvine, CA, United States,

18 Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German Chronic Lymphocytic Leukemia Study Group, University of Cologne, Cologne, Germany,

19 Sir Charles Gairdner Hospital, Division of Haematology, Nedlands, Western Australia, Australia,

20 Medical School, University of Western Australia, Division of Internal Medicine, Perth, Western Australia, Australia,

21 Eli Lilly and Company, Indianapolis, United States,

22 University of Texas MD Anderson Cancer Center, Houston, TX,

Abstract:

Introduction: Covalent Bruton tyrosine kinase inhibitors (cBTKi) are a mainstay of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treatment. Pirtobrutinib is a highly selective, non-covalent BTKi with proven efficacy in CLL/SLL patients (pts) previously treated with a cBTKi. We report results from the first head-to-head comparison of pirtobrutinib versus ibrutinib in treatment-naïve (TN) pts and pts with cBTKi-naive relapsed/refractory (R/R) CLL/SLL (NCT05254743).

Methods:

Eligible pts were randomized 1:1 to receive pirtobrutinib (200 mg QD) or ibrutinib (420 mg QD), stratified by del(17p) status and number of prior lines of therapy (0 vs 1 vs ≥ 2). Treatment was administered until progression or development of unacceptable toxicity. Primary endpoints were non-inferiority (NI) of overall response rate (ORR; partial response or better by independent review committee [IRC]/iwCLL 2018), in intent-to-treat (ITT) and R/R populations, with ORR ratio NI margins of 0.88 and 0.86, respectively. PFS was a secondary endpoint to be tested for superiority at a future timepoint. We present the final ORR analyses in ITT and R/R populations, and descriptive analyses of secondary endpoints, including in the TN population, using a 10June2025 data cut.

Results:

From 18August2022 to 17June2024, 662 pts were randomized to receive pirtobrutinib (n=331) or ibrutinib (n=331). For both arms, the median age was 67 (pirtobrutinib range, 39-90; ibrutinib, 34-86), and the median number of prior therapies was 1. The ITT population included 225 TN and 437 R/R pts. Among pirtobrutinib vs ibrutinib pts with evaluable samples, unmutated IGHV was 68% (199/293) vs 66% (183/277), complex karyotype ≥3 abnormalities was 40% (104/259) vs 34% (78/227), and del(17p) was 15% (50/331) vs 16% (52/331), respectively. The study met its primary endpoint demonstrating statistically significant NI of ORR of pirtobrutinib vs ibrutinib in both the ITT population (87.0% [95%CI,82.9-90.4] vs 78.6% [95%CI,73.7-82.9]; ORR ratio=1.11 [95%CI,1.03-1.19]; 2-sided p<0.0001) and R/R population (84.0% [95%CI,78.5-88.6] vs 74.8% [95%CI,68.5-80.4]; ORR ratio=1.12 [95%CI,1.02-1.24]; 2-sided p<0.0001), respectively. In the TN population, ORR was 92.9% (95%CI,86.4-96.9) with pirtobrutinib vs 85.8% (95%CI,78.0-91.7) with ibrutinib. ORR consistently favored pirtobrutinib vs ibrutinib across subgroups in both the ITT and R/R population, including del(17p) (ITT, 80.0% vs 75.0%; R/R, 80.6% vs 80.0%) and without del(17p) (ITT, 88.3% vs 79.2%; R/R, 84.7% vs 73.8%). PFS data were not yet mature, but favored pirtobrutinib in ITT (HR, 0.57 [95%CI,0.39-0.83]), R/R (HR, 0.73 [95%CI,0.47-1.13]), and TN (HR, 0.24 [95%CI,0.10-0.59]) pts, with a median follow up of 21.8 months, 18.2 months, and 22.5 months, respectively. The 18-month PFS rates (95%CI) in pirtobrutinib and ibrutinib arms were86.9% (82.4-90.3) vs 82.3% (77.3-86.3) in ITT, 81.7% (75.1-86.7) vs 79.2% (72.3-84.6) in R/R, and 95.3% (89.1-98.0) vs 87.6% (79.7-92.6) in TN, respectively. There was no detriment in overall survival (HR, 0.961 [95%CI,0.55-1.69]) for the ITT population. The most common treatment-emergent adverse events were similar between arms. Adverse events (AE) of interest, such as atrial fibrillation/flutter occurred in 2.4% of pirtobrutinib and 13.5% of ibrutinib pts; hypertension in 10.6% and 15.1% of pts, respectively. Fewer AE-related dose reductions were seen with pirtobrutinib (7.9%) vs ibrutinib (18.2%). Treatment discontinuation due to progressive disease was more common with ibrutinib (pirtobrutinib, n=15 [4.5%] vs ibrutinib, n=36 [10.9%]), and similar for AE (pirtobrutinib, n=26 [7.9%] vs ibrutinib, n=24 [7.3%]). Treatment is ongoing in 81.3% of pirtobrutinib and 69.5% of ibrutinib pts.

Conclusion:

In this first head-to-head study, in cBTKi-naïve CLL/SLL, including pts with treatment naïve CLL, pirtobrutinib demonstrated NI of ORR vs ibrutinib in both ITT and R/R populations. PFS, while not yet mature, trended in favor of pirtobrutinib, with the most pronounced effect in the TN population, which had the longest follow-up at this data cut.

Jennifer Woyach AJ Oncology ASH 2025

Alexis Ann LeVee MD; 2025 SABCS: Pre-Operative Gut Microbiome Predicts Complete Response to Immune Checkpoint Inhibition in Patients with Early-stage HER2-positive Breast Cancer

Audio Medica News — Thu, 22 Jan 2026 13:19:04 +0000

Alexis Ann LeVee MD; 2025 SABCS: Pre-Operative Gut Microbiome Predicts Complete Response to Immune Checkpoint Inhibition in Patients with Early-stage HER2-positive Breast Cancer

An interview with:

Alexis Ann LeVee MD, Clinical Instructor of Medicine, UCLA David Geffen School of Medicine, Los Angeles, USA.

SAN ANTONIO, USA—New evidence that what patients eat can have a strong influence on the effectiveness of their cancer treatment was illustrated by new research on the microbiome reported at the 2025 San Antonio Breast Cancer Symposium.

The conference saw results from the randomized phase II neoHIP trial looking at microbiome bacterial profiles in patients with HER2-positive early breast cancer at a poster from Alexis LeVee MD of the UCLA David Geffen School of Medicine in Los Angeles. During the session she talked about the results with Audio Journal of Oncology reporter, Peter Goodwin:

POSTER TITLE

Gut microbiome composition predicts pathologic complete response in patients with early-stage HER2-positive breast cancer receiving neoadjuvant HER2-targeted therapy +/- immunotherapy with pembrolizumab

SPEAKER:

Alexis LeVee, UCLA David Geffen School of Medicine, Los Angeles, CA

AUTHORS:

LeVee1, K. Lee2, S. Rice3, I. Chan3, S. Sridharan3, S. Shiao4, S. Pal5, H. McArthur3; 1Department of Medicine, Division of Hematology and Oncology, UCLA David Geffen School of Medicine, Los Angeles, CA, 2TGen Integrated Microbiomics Center (TIMC), Translational Genomics Research Institute (TGen), Flagstaff, AZ, 3Department of Medicine, Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, TX, 4Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, 5Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA.

Background:

The gut microbiome has been shown to influence response to immune checkpoint inhibitors (ICI). This study aimed to investigate the association between gut microbiome profiles and clinical outcomes in patients with early-stage HER2-positive (HER2+) breast cancer receiving neoadjuvant HER2-targeted therapy +/- immunotherapy with pembrolizumab (K) as part of the randomized phase II neoHIP trial. Methods: Patients with stage II-III HER2+ breast cancer were randomized to 3 treatment arms: Arm A consisted of paclitaxel (T), trastuzumab (H), and pertuzumab (P), THP; Arm B of THP-K; and Arm C of TH-K. Fecal samples were collected at baseline, cycle 3 day 1, surgery, and at 30 and 60 days post-surgery and were analyzed using deep shotgun metagenomics sequencing. Pre-operative fecal samples were analyzed according to pathologic complete response (pCR) and onset of diarrhea during the neoadjuvant period. Comparisons were adjusted to control for false discovery rates (q-value).

Results:

99 fecal samples (Arm A: n=32; Arm B: n=48; Arm C: n=19) from 27 patients were included in the analysis. Bacterial diversity by Jaccard analysis was significantly different across all time points for all arms (all p<0.05; q<0.05). In the THP and THP-K arms, Jaccard analysis demonstrated differences in gut microbiome diversity in patients who achieved pCR versus non-pCR (p=0.009; q=0.009). In patients treated with THP who achieved pCR, multiple species were in greater abundance including GGB9237 SGB14179 (log fold change [LFC] 6.87), GGB34797 SGB14322 (LFC 6.25), and Faecalicatena fissicatena (LFC 4.61) compared to those with non-pCR (all p<1E-5; q<0.01). In the THP-K arm, patients who achieved pCR had different species in greater abundance, including GGB9365 SGB14341 (LFC 3.15), Hydrogenoanaerobacterium saccharovorans (LFC 2.92), and GGB9502 SGB14899 (LFC 2.56) compared to those with non-pCR (all p<0.0001; q<0.01). Comparing those who achieved pCR in THP vs. THP-K, GGB9715 SGB15260 (LFC 4.89), Brotolimicola acetigignens (LFC 4.88), and Clostridiaceae bacterium Marseille Q4149 (LFC 4.54) were higher in abundance in the THP-K arm, and GGB34797 SGB14322 (LFC 6.27) and GGB3175 SGB4191 (LFC 5.73) were depleted in the THP-K arm (all p<0.0001; q<0.05). In patients with diarrhea vs. without diarrhea, beta diversity was significantly different in the THP arm by Bray Curtis analysis (p<0.05; q<0.05) and in the THP-K arm by Jaccard analysis (p<0.05; q<0.05), with multiple species in different abundances in those with and without diarrhea in both arms (p<0.05). Conclusion:

This is the first study to demonstrate that the pre-operative gut microbiome influences response to ICI in patients with early-stage HER2+ breast cancer. Patients who achieved pCR had a significantly different microbiome profile compared to those with residual disease. This study highlights the role of the gut microbiome in influencing response to ICI in patients with breast cancer treated in the curative intent setting.

Alexis Ann LeVee 2025 SABCS AJOncology

Meletios Dimopoulos; ASH 2025: B-Cell Maturation Antigen Bispecific Antibody Linvoseltamab Brings High Response Rates in Patients with Relapsed/Refractory Multiple Myeloma

Audio Medica News — Tue, 20 Jan 2026 22:53:50 +0000

B-Cell Maturation Antigen Bispecific Antibody Linvoseltamab Brings High Response Rates in Patients with Relapsed/Refractory Multiple Myeloma

An interview with:

Meletios-Athanasios C. Dimopoulos MD, Professor and Chair, Department of Clinical Therapeutics (Alexandra Hospital), School of Medicine, University of Athens, Greece.

ORLANDO, USA—The bispecific monoclonal antibody linvoseltamab achieved high rates of clinical response when used in combination with anti-CD 38 therapy in patients who had relapsed/refractory multiple myeloma. Early findings on efficacy and safety from the phase 1b LINKER-MM2 trial were announced at the 2025 Annual Meeting of the American Society of Hematology by Meletios Dimopoulos MD, Chair of Clinical Therapeutics at the University of Athens in Greece. Peter Goodwin caught up with him just after his talk:

Audio Journal of Oncology: Meletios-Athanasios C. Dimopoulos MD

IN: [GOODWIN]I am here at the American….

OUT: ….. Journal of Oncology, I’m Peter Goodwin. 8:20 secs

2025 ASH Abstract 2254

Safety and efficacy of linvoseltamab (LINVO) combined with anti-CD38 monoclonal antibodies (mAbs) daratumumab (DARA) or isatuximab (ISA) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Initial results from the multicohort, Phase 1b LINKER-MM2 trial

ASH ABSTRACT: 2254

Title :

“Safety and efficacy of linvoseltamab (LINVO) combined with anti-CD38 monoclonal antibodies (mAbs) daratumumab (DARA) or isatuximab (ISA) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Initial results from the multicohort, Phase 1b LINKER-MM2 trial”

Poster Abstract Session, Speaker: Meletios Dimopoulos, MD

Authors

Meletios Dimopoulos 1, Sosana Delimpasi2, Salomon Manier3, Jean-Marie Michot4, Enrique Ocio5, Samuel Rubinstein6, Joselle Cook7, Maria Del Carmen Martinez Chamorro8, Aurora Breazna9, Amishi Dhadwal9,Yogita Ghodke9, Sheila Masinde9, Glenn Kroog9, Shawn Sarkaria9, Albert Oriol10

Institutions:

1 Alexandra General Hospital, National and Kapodistrian University of Athens, Athens, Greece, 2Department of Hematology and Bone Marrow Transplantation Unit, General Hospital Evangelismos, Athens, Greece, 3 Hematology Department, Lille University Hospital, Lille, France, 4 Gustave Roussy Cancer Campus, Villejuif, France, 5 Servicio de Hematología y Hemoterapia, Hospital Universitario Marqués de Valdecilla University Hospital (IDIVAL) Universidad de Cantabria Santander, Santander, Spain, 6 Department of Hematology/Oncology, University of North Carolina, Chapel Hill, NC, United States, 7

Mayo Clinic, Rochester, MN, United States, 8 Hematology Department, Hospital Universitario Quirónsalud Madrid and Universidad Europea de Madrid, Madrid, Spain, 9 Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States, 10 Department of Hematology, Institut Català d’Oncologia i Institut Josep Carreras Hospital Germans Trias i Pujol, Badalona, Spain

Phase 1b LINKER-MM2 trial (NCT05137054).

Introduction

LINVO, a human B-cell maturation antigen (BCMA)xCD3 bispecific antibody, was recently approved for triple-class exposed (TCE) RRMM after ≥3 prior therapies (EU) or ≥4 prior lines of therapy (US), demonstrating high efficacy and a generally manageable safety profile. Combining LINVO with an anti-CD38 mAb, such as DARA or ISA, may provide additional benefit to pts with RRMM. Here we report pooled safety and efficacy results from the LINVO + DARA and LINVO + ISA cohorts during the dose-finding portion of the Phase 1b LINKER-MM2 trial (NCT05137054).

Methods

Eligible pts were aged ≥18 years with RRMM that progressed after ≥3 lines of therapy (LoTs), or ≥2 LoTs if TCE or double-class refractory (immunomodulatory drug [IMiD] + proteasome inhibitor [PI]). Prior treatment (tx) with DARA or ISA was allowed if previously tolerated and ≥6 months (mos) or ≥3 mos washout, respectively, had elapsed since last exposure. Tx began with LINVO monotherapy (Cycle [C]0; 28-day cycle) consisting of 2 step-up doses (5 mg, 25 mg) and 2 full doses (dose level [DL]1 100 mg; DL1b 150 mg; DL2 200 mg) before standard dosing of DARA or ISA was added at C1. LINVO was given once weekly in C1–3 and once every 2 weeks in C4+. At the end of 2024, dosing once every 4 weeks was implemented after C6 if a very good partial response or better (≥VGPR) was achieved. Dexamethasone premedication was required during the first 2 cycles and then given per label for DARA or ISA. Primary endpoints: dose-limiting toxicities (DLTs) and tx-emergent adverse events (TEAEs). Key secondary endpoints: overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and rate of minimal residual disease (MRD) negativity. The analyses reported here combine the LINVO + DARA and LINVO + ISA cohorts.

Results

As of May 7, 2025, 42 pts were enrolled. All pts were included in the safety analysis set: DL1 (DARA, n=12; ISA, n=6), DL1b (n=6; n=10), or DL2 (n=8; n=0); 37 were included in the efficacy analysis set: DL1 (DARA, n=11; ISA, n=5), DL1b (n=5; n=9), or DL2 (n=7; n=0). At baseline, all pts had received ≥1 PI (refractory to ≥1 PI: 76%) or ≥1 IMiD (refractory to ≥1 IMiD: 86%), and 21 pts (50%) had received prior DARA or ISA (refractory to DARA or ISA: 33% [DARA, n=4; ISA, n=10]). Median number of prior LoTs was 3 (range 2–8), including 50% of pts with TCE and 21% with triple-class refractory disease. Median age was 68 years (range 42–86); male, 57%; ISS stage III at study entry, 12%; high-risk cytogenetics, 31%; bone marrow plasma cells ≥50%, 31%; and soft tissue plasmacytomas, 33% (extramedullary, 12%). Median follow-up duration was 14.8 mos for DL1 (DARA 21.3; ISA 11.3), 7.6 mos for DL1b (DARA 13.5; ISA 5.2), and 5.9 mos for DL2 (all DARA), with 44%, 50%, and 63% of pts still receiving tx, respectively. The most common TEAEs were anemia (any grade [Gr] 48%; Gr 3/4 26%), neutropenia (41%; 41%), diarrhea (38%; 2%), and thrombocytopenia (38%; 17%). Cytokine release syndrome was reported in 33% of pts (all Gr 1/2 events except 1 Gr 3 event during the step-up period that fully resolved). No pts experienced immune effector cell-associated neurotoxicity syndrome (ICANS). Infections were reported in 32 pts (any Gr 76%; Gr ≥3 40%), and 3 resulted in death (1 tx related: cytomegalovirus [CMV] pneumonia; 2 tx unrelated: C. diff colitis and lower respiratory infection). One DLT was observed at DL1b in the ISA cohort (Gr 3 Epstein–Barr virus pharyngitis) and 1 was observed at DL2 in the DARA cohort (Gr 5 CMV pneumonia). Among efficacy evaluable pts, ORR was 75% at DL1 (12/16; ≥VGPR rate 75%), 93% at DL1b (13/14; ≥VGPR rate 57%), and 86% at DL2 (6/7; ≥VGPR rate 86%). Of 10 MRD-evaluable pts, all were MRD negative (<10−5by clonoSEQ or EuroFlow). The 12-mo DOR rate was 79% (95% confidence interval [CI] 52–92; median DOR not reached) and 12-mo PFS rate was 73% (95% CI 53–86; median PFS not reached). Pharmacokinetic analyses showed LINVO concentrations were not affected by the addition of DARA or ISA.

Conclusions:

In pts with heavily pretreated RRMM, half of whom had prior anti-CD38 mAb exposure, the combination of LINVO and DARA or ISA was feasible, inducing a high rate of deep and durable responses, and exhibiting a safety profile similar to that reported for each individual drug. These preliminary data support continued development of LINVO plus an anti-CD38 mAb for the tx of pts with MM.

ASH 2025 Audio Journal of Oncology: Meletios-Athanasios C. Dimopoulos. Posted January 21, 2026

Antonio Jimenez Jimenez MD MS; ASH 2025: Donor Choice No Longer a Barrier to Allogeneic Stem Cell Transplantation for Patients with Hematologic Malignancies

Audio Medica News — Mon, 19 Jan 2026 10:42:47 +0000

Antonio Jimenez Jimenez MD MS; ASH 2025: Donor Choice No Longer a Barrier to Allogeneic Stem Cell Transplantation for Patients with Hematologic Malignancies

An interview with:

Antonio Jimenez Jimenez MD MS, Associate Professor of Medicine, Division of Transplantation and Cellular Therapy, University of Miami Miller School of Medicine, Sylvester Cancer Center, Co-Chair National Marrow Donor Program Access Trial, Miami, FL, United States

ORLANDO, USA—A wider, more ethnically diverse range of patients could safely receive allogeneic hematopoietic cell transplantations from unrelated donors according to findings from the USA-based National Marrow Donor Program Access Trial reported at the 2025 Annual Meeting of the American Society of Hematology.

The use of post-transplant cyclophosphamide appears to be levelling the playing field for patients who do not have access to a fully matched donor, according to Antonio Jimenez Jimenez MD MS, from the University of Miami Miller School of Medicine, who co-chairs the National Marrow Donor Program Access Trial. After telling the conference about his new data he gave the details to the Audio Journal of Oncology’s Peter Goodwin:

Audio Journal of Oncology: Antonio Jimenez Jimenez MD MS

IN [GOODWIN]”Here from the American Society of ….

OUT: …..I’m Peter Goodwin 10:58secs

REFERENCE:

https://ashpublications.org/blood/article/146/Supplement%201/936/552282/Mismatching-of-unrelated-donors-beyond-a-single

ASH 2025 Abstract Number: 936

ABSTRACT TITLE :

Mismatching of unrelated donors beyond a single HLA-locus does not adversely impact outcomes at one year following transplantation: Results from the NMDP sponsored ACCESS study

(Category: 700s – Transplantation and Adoptive Cell Therapies

Review Category: 722. Allogeneic Transplantation: Acute and Chronic GVHD and Immune Reconstitution)

AUTHORS

Monzr M. Al Malki1, Stephanie Bo-Subait2, Brent Logan3, 4, Sarah Smith2, Erin Leckrone2, Heather Stefanski2, Jeffery Auletta2, Stephen Spellman2, Craig Malmberg2, Medhat Askar2, 5, Rachel Cusatis4, Brian Shaffer6, Dipenkumar Modi7, Farhad Khimani8, Mahasweta Gooptu9, Mehdi Hamadani4, Martin Maiers2, Joseph Stanek2, Javier Meade10, Uttam Rao11, Jordan Milner12, Ramzi Abboud13, Katarzyna Jamieson14, George Carrum15, Bhagirathbhai Dholaria16, William Hogan17, Ran Reshef18, Satyajit Kosuri19, Rachel Cook20, Karen Ballen21, Alison Loren22, Karilyn Larkin23, Sally Arai24, Muna Qayed25, Sung Choi26, Larisa Broglie4, 27, Bronwen Shaw4, Steven Devine2, Antonio Jimenez Jimenez28

INSTITUTIONS:

1 City of Hope National Medical Center, Duarte, CA, United States, 2 CIBMTR® (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, MN, United States, 3 Division of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee, WI, United States, 4 CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of

Wisconsin, Milwaukee, WI, United States, 5 Health Sector & College of Medicine, Qatar University, Doha, Qatar, 6 Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 7 Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States, 8 Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, United States, 9 Department of Hematology/Oncology, Dana-Farber Cancer Institute, Boston, MA, United States, 10 Division of Hematologic Malignancies, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Boston, MA, United States, 11 Sarah Cannon Transplant and Cellular Therapy Program at St. David’s South Austin Medical Center, Austin, TX, United States, 12 Shands HealthCare & University of Florida, Gainesville, FL, United States, 13 Washington University in St. Louis School of Medicine, St. Louis, United States, 14 University of North Carolina Hospitals, Chapel Hill, NC, United States, 15 Baylor College of Medicine Center for Cell and Gene Therapy, Baylor College of Medicine-Methodist Hospital, Houston, TX, United States, 16 Vanderbilt University Medical Center, Nashville, TN, United States, 17 Division of Hematology/BMT, Mayo Clinic, Rochester, MN, United States, 18 Blood and Marrow Transplant and Cell Therapy Program, Columbia University Irving

Medical Center, New York, NY, United States, 19 University of Chicago Medicine, Chicago, IL, United States, 20 Knight Cancer Institute, Oregon Health & Science University, Portland, MN, United States, 21 Division of Hematology/Oncology, University of Virginia Health, Charlottesville, VA, United States, 22

Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States, 23 The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States, 24 Stanford Health Care, Palo Alto, CA, United States, 25 Aflac Cancer and Blood Disorders Center, Emory University and Children’s Healthcare of Atlanta, Atlanta,

GA, United States, 26 University of Michigan, Blood and Marrow Transplantation Program, Ann Arbor, MI, United States, 27 Division of Pediatric Hematology/Oncology/Blood and Marrow Transplant, Department

of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States, 28 Division of Transplantation and Cellular Therapy, University of Miami Miller School of Medicine, Miami, FL, United States

ABSTRACT

Allogeneic hematopoietic cell transplantation (HCT) remains inaccessible to many patients, particularly those of non-European ancestry, due to the limited availability of matched unrelated donors (URD). While single-HLA mismatched donors (7/8) often yield acceptable outcomes, URD HCT mismatched at ≥ 2 HLA alleles (<7/8) has historically been associated with poor survival and prohibitive toxicity. Post-transplant cyclophosphamide (PTCy) has improved outcomes following mismatched unrelated donor (MMUD) HCT, potentially enabling less stringent donor matching. Whether the degree of donor-recipient HLA disparity remains prognostic after MMUD HCT when PTCy is used is unknown. The ACCESS trial (NCT04904588) was conducted by the Center for International Blood and Marrow Transplant Research Clinical Research Organization and prospectively evaluated PTCy-based graft versus host disease (GVHD) prophylaxis in adult recipients of 4–7/8 (HLA-A, -B, -C and -DRB1) MMUD peripheral blood stem cells (PBSC) from donors age ≤35 years old following either myeloablative (MAC) or reduced intensity/non-myeloablative (RIC/NMA) conditioning. This analysis focused on all adult recipients of <7/8 grafts enrolled on the study across both conditioning strata, with descriptive comparison to patients who received 7/8 MMUD PBSC grafts.

The primary endpoint was 1-year overall survival (OS). Secondary endpoints included primary graft failure (PGF), non-relapse mortality (NRM), relapse, acute and chronic GVHD, and GVHD-free relapse-free survival (GRFS).

A total of 268 adults received MMUD PBSC grafts: 85 with <7/8 matches (MAC: n=23; RIC/NMA: n=62) and 183 with 7/8 matches (MAC: n=52; RIC/NMA: n=131). Among <7/8 recipients, median age was 57 years old (range, 24–78), 49% were male, with diagnoses of acute myeloid leukemia (AML) (55%), myelodysplastic syndromes (MDS) (15%), and lymphoma (14%). HLA mismatch distribution in the <7/8 group was 6/8 in 82%, 5/8 in 14%, and 4/8 in 4%. Most received fludarabine/melphalan (44%) or myeloablative busulfan/fludarabine (21%). Median CD34+ cell dose was 5.5 ×10^6/recipient kg (range: 3.2-8.0) and 75% of grafts were cryopreserved prior to infusion. Median donor age was 25.8 (range: 18.7-35.7) in the 7/8 group and 25.0 (range: 18.3-34.8) in the <7/8 group. The <7/8 cohort was racially and ethnically diverse, with 61% identifying as other than non-Hispanic white. The 7/8 cohort had a median age of 63 years old (range, 20–79), with 52% male. Disease distribution, conditioning intensity, and infused cell doses were similar to the <7/8 group. A smaller proportion of grafts were cryopreserved (61%), and 47% of patients identified as other than non-Hispanic White.

One-year OS for <7/8 recipients was 86% (95% CI: 76–92%), compared to 79% (95% CI: 72–84%) in 7/8 recipients. One-year incidence of relapse was 23% (95% CI: 14–33%) in the <7/8 group and 17% (95% CI: 12–23%) in 7/8 recipients; NRM was 8% (95% CI: 4–16%) and 14% (95% CI: 9–19%), respectively. GRFS was 55% (95% CI: 43–65%) for <7/8 and 51% (95% CI: 44–58%) for 7/8 recipients.

PGF occurred in 8% (95% CI: 3–18%) of <7/8 RIC recipients and 3% (95% CI: 1–8%) of 7/8 RIC recipients; no MAC recipients had PGF. At 6 months post-HCT, grade II–IV acute GVHD occurred in 34% (95% CI: 24–44%) of <7/8 patients and 39% (95% CI: 32–46%) of 7/8; grade III–IV acute GVHD was observed in 7% (95% CI: 3–14%) and 8% (95% CI: 5–13%), respectively. Moderate to severe chronic GVHD (NIH consensus criteria) at one year occurred in 8% (95% CI: 3–15%) of <7/8 recipients and 11% (95% CI: 7–16%) of 7/8 recipients.

When grouped by conditioning intensity, 1-year outcomes within the <7/8 cohort were: OS 91% after MAC and 84% after RIC/NMA; relapse in 32% after MAC and 20% after RIC/NMA, respectively; GRFS was 53% for MAC and 55% for RIC/NMA; and NRM remained low at 9% after MAC and 8% after RIC/NMA.

In this cohort of adult recipients of <7/8 MMUD PBSC grafts with PTCy-based GVHD prophylaxis enrolled on the ACCESS study, 1-year OS exceeded 80% and was comparable to 7/8 recipients. Relapse, NRM, and GVHD rates were similarly favorable and consistent with outcomes reported in 7/8 donor recipients. These findings support extending suitable MMUD match considerations to include 4-6/8 in the context of PTCy, potentially enabling near-universal donor access, while allowing for optimization of other non-HLA donor factors.

AUDIO JOURNAL OF ONCOLOGY January 19, 2025

Safna Naozer Virji MBBS FPBS; 2025 SABCS: Oncoplastic Breast Cancer Surgery Study Reports High Efficacy with Superior Psychosocial Outcomes in a Low or Middle Income Country Setting

Audio Medica News — Fri, 16 Jan 2026 07:49:42 +0000

Safna Naozer Virji MBBS FPBS; 2025 SABCS: Oncoplastic Breast Cancer Surgery Study Reports High Efficacy with Superior Psychosocial Outcomes in a Low or Middle Income Country Setting

An interview with:

Safna Naozer Virji MBBS FPBS

Breast Surgery Fellow, Aga Khan University Hospital, Karachi , Pakistan

SAN ANTONIO, USA—Breast cancer surgeons can deliver high levels of satisfaction to worried patients without sacrificing efficacy in resource-limited settings in a low or middle income country, according to research from Pakistan reported at the 2025 San Antonio Breast Cancer Symposium.

Safna Naozer Virji MBBS FPBS, who is a Breast Surgery Fellow at the Aga Khan University Hospital in Karachi, Pakistan, gave a poster presentation at the conference reporting the outcome of a large series of procedures conducted at her center. Audio Journal of Oncology reporter Peter Goodwin caught up with her at her poster to find out more:

Audio Journal of Oncology: Safna Naozer Virji MBBS FPBS

IN: [Goodwin] “I’m talking now to …

OUT: ……Journal of Oncology. I’m Peter Goodwin

7: 58”

Source:

Poster Session 2, Day 2: December 10, 2025, San Antonio Breast Cancer Symposium

Presentation number: PS2-03-04

TITLE:

Re-defining Breast Cancer care in an LMIC- a single center study on long term oncological and cosmetic outcomes of Oncoplastic Breast Surgery

SPEAKER:

Safna Naozer Virji, Aga Khan University Hospital, Karachi, Karachi, Pakistan

AUTHORS:

N. Virji, L. Vohra, S. Khan, I. Khan; Breast Surgery, Department of Surgery, Aga Khan University Hospital, Karachi, Karachi, PAKISTAN.

Background:

Surgical management has greatly evolved from a radical mastectomy to the most recent advancement of a more conservative oncoplastic breast surgery (OBS). It has not only proven to be safe, but also has shown superior cosmetic outcomes compared to standard breast conservation surgery as it is able to address larger and even multi-focal tumors. Nevertheless, this is a relatively novel concept in our developing country with a limited number of professionals trained in the field. Furthermore, there is a financial aspect and stigma to take into consideration. Patients have to pay out of pocket for treatment which deters them from risking the possibility of a second surgery – in case of incomplete resection margins. It also adds the burden on the surgeon to deliver optimal cosmetic outcomes with no intervention to the contralateral breast. The purpose of this study is to determine the long-term oncological and cosmetic outcomes of patients with early-stage breast cancer who underwent OBS at our institution. Methodology: A single-center retrospective study was conducted on adult female patients with biopsy proven Stage I to III breast cancer who underwent OBS from January 2017 to June, 2022. Patients who underwent bilateral breast surgery were excluded. A total of 194 women were eligible for the study and data was extracted from patient records to determine the long term oncologic outcomes— breast cancer recurrence, disease-free survival (DFS), and overall survival (OS). Cosmetic outcomes were evaluated via patient-reported satisfaction using the Harvard breast cosmesis scale, through telephonic interview after obtaining informed verbal consent. The study was approved by the institutional Ethical Review Committee (ERC 2025-11482-34955). Results:

The mean age of women at diagnosis was 48.3 ± 13.2 years with 81% having invasive ductal carcinoma. Sixty-seven percent of the women had hormone receptor positive breast cancer, while 20% had triple negative disease. Among all the patients who were included in the study, half of the patients received neoadjuvant chemotherapy before OBS, followed by adjuvant radiation therapy. Of note, only 6 (3.1%) out of 194 women had a positive margin for which they underwent a second procedure. Level 1 OBS was performed among 77% of the patients. Among those who underwent Level 2 OBS a variety of local perforator flaps were performed. We had a 68% response rate among the patients who were approached via telephone to determine the self-reported cosmetic outcomes, with 91% of the participants reporting ‘Good’ (51%) or ‘Excellent’ (40%) cosmetic outcomes when compared to the contralateral breast. Eight (4.1%) out of 16 patients had an ipsilateral recurrence, while the remaining developed distant metastases. The Kaplan Meier analysis showed that the mean OS of the study participants was 96 months (95% CI=92.2-99.7) since diagnosis, with death as the outcome event. The mean DFS was 93 months (95% CI=89.5 – 97.6) since diagnosis until recurrence as the outcome event. There were significant differences in survival times for patients by recurrence (log rank test, p=0.000) and hormone receptor status (log rank test, p=0.015). There was no significant difference in survival times for patients by type of OBS (log rank test, p=0.860).

Conclusion:

Oncoplastic breast surgery is a safe and effective option for early-stage breast cancer, with low margin positivity and favorable long-term outcomes. Our study demonstrates excellent survival and high patient-reported cosmetic satisfaction, especially with Level 1 OBS. These findings support its broader use—even in resource-limited settings—as a balanced approach to oncologic safety and aesthetic outcomes.

AJOncologyhttps://www.audiomedica.com/wp-content/2026/01/Safna-Naozer-Virji-SABCS-AJO-PRODUCTION-MASTER.mp3, January 16, 2026

Luciano Costa, MD PhD; ASH 2025: CAR T Cell Brings Profound Benefit with Long-Term Progression-Free Survival in Patients with Standard-Risk Relapsed/Refractory Multiple Myeloma

Audio Medica News — Wed, 14 Jan 2026 16:27:35 +0000

Luciano Costa, MD, PhD; ASH 2025: CAR T Cell Brings Profound Benefit with Long-Term Progression-Free Survival in Patients with Standard-Risk Relapsed/Refractory Multiple Myeloma

An interview with:

Luciano Costa, MD PhD, University of Alabama at Birmingham, Birmingham, Alabama, United States

ORLANDO, USA—The CARTITUDE-4 study has f0und that patients with standard-risk relapsed or refractory multiple myeloma can benefit greatly from ciltacabtagene autoleucel CAR-T cell therapy after one to three prior lines of therapy, as do those with high-risk disease. Study findings were reported at the American Society of Hematology 2025 Annual Meeting in Orlando Florida by Luciano Costa, MD, PhD, University of Alabama, in Birmingham, Alabama, USA. After his talk at the conference he discussed the findings with the Audio Journal of Oncology reporter, Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Luciano Costa MD PhD

IN: [Goodwin] “I’m right here at the ……

OUT: …. In Orlando, Florida. 13:04 secs

JOURNAL ARTICLE:

Reference: Blood:

Volume 146, Supplement 1, 3 November 2025, Page 94

LINK:

https://www.sciencedirect.com/science/article/pii/S0006497125026692

TITLE:

Long-term progression-free survival benefit with ciltacabtagene autoleucel in standard-risk relapsed / refractory multiple myeloma

First author: Luciano Costa

Authors:

University of Alabama at Birmingham, Birmingham, United StatesLuciano Costa 1, Albert Oriol 2, Dominik Dytfeld 3, Salomon Manier 4, Peter Voorhees 5,

Yi Lin 6, Myo Htut 7, Wilfried Roeloffzen 8, Phoebe Joy Ho 9, Urvi Shah 10, Man Zhao 11, Quanlin Li 12, Agnes Balogh 13, Katherine Li 14, Ana Slaughter 15, Nina Benachour 13, Carolina Lonardi 16, Arnab Ghosh 17, Huabin Sun 17, Nikoletta Lendvai 17, Tamar Lengil 17, Nitin Patel 18, Mythili Koneru 18, Erika Florendo 18, Octavio Costa 18, Vrinda Mahajan 18, Paula Rodriguez Otero 19, Christopher Strouse 20, Keith Stewart 21, Surbhi Sidana 22

Institutions:

1.University of Alabama at Birmingham, Birmingham, United States

2Institut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain

3Poznan University of Medical Sciences, Poznań, Poland

4University of Lille, CHU Lille, Lille, France

5Atrium Health/Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, United States

6Mayo Clinic, Rochester, United States

7Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, United States

8Department of Hematology, University Medical Center Groningen, Groningen, Netherlands

9Royal Prince Alfred Hospital, Sydney, Australia

10Myeloma Service, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York, United States

11IQVIA, Shanghai, China

12Johnson & Johnson, Apex, United States

13Johnson & Johnson, Beerse, Belgium

14Johnson & Johnson, Spring House, United States

15Johnson & Johnson, Zug, Switzerland

16Johnson & Johnson, Buenos Aires, Argentina

17Johnson & Johnson, Raritan, United States

18Legend Biotech USA Inc, Somerset, United States

19Cancer Center Clínica Universidad de Navarra, Cima, Pamplona, Spain

20Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, United States

21University Health Network and the Princess Margaret Cancer Centre, Toronto, ON, Canada

22Stanford University School of Medicine, Stanford, United States

ASH Abstract Presentation ID 94

Introduction: The CARTITUDE-4 study (NCT04181827), which enrolled patients with lenalidomide-refractory multiple myeloma (MM) after 1–3 prior lines of therapy (pLOT), demonstrated a significant benefit of ciltacabtagene autoleucel (cilta-cel) over established triplet regimens. However, the benefit of cilta-cel for patients with standard-risk cytogenetics remains less defined. Here, we report outcomes in patients with standard-risk cytogenetics from the intent-to-treat and as-treated populations in CARTITUDE-4.

Methods: InCARTITUDE-4, patients randomized to the cilta-cel arm underwent apheresis and bridging treatment with either pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd), followed by lymphodepletion therapy with cyclophosphamide and fludarabine, and then a single cilta-cel infusion. Progression-free survival (PFS) was assessed using a validated computerized algorithm. The intent-to-treat population included 208 patients; 32 patients progressed or died on bridging therapy, resulting in an as-treated population of 176 patients. Patients with high-risk cytogenetics, defined as del(17p), t(14;16), t(4;14), gain/amp(1q) (n=105), or with unknown cytogenetics (n=12), were excluded from the as-treated analysis. The 12-month minimal residual disease (MRD)-negative complete response (CR) was defined per the International Myeloma Working Group criteria as the proportion of participants with CR or better prior to and at 12 months (±3 months), achieving MRD-negative status at 12 months (+3 months) after cilta-cel infusion, as determined by next-generation sequencing (10-5), prior to progressive disease or subsequent anti-myeloma therapy. For the as-treated population, PFS rates were measured from the time of cilta-cel infusion.

Results: In CARTITUDE-4, in the intent-to-treat population, at a median follow-up of 33.6 months, patients with standard-risk cytogenetics had a 30-month PFS rate (95% CI) of 71.0% (58.8–80.2) in the cilta-cel arm (N=69) vs 43.2% (31.3–54.5) in the standard-of-care (SOC) arm (N=70). Patients with standard-risk cytogenetics in the as-treated population (n=59) had a 30-month PFS rate of 80.5% (95% CI, 67.2–88.8). In CARTITUDE-1 (NCT03548207), which evaluated cilta-cel in patients with heavily pretreated relapsed/refractory MM (RRMM; ≥3 pLOT), the 30-month PFS rate among patients with standard-risk cytogenetics (negative for del(17p), t(14;16), or t(4;14); n=68) was 59.9% (95% CI, 47.2–70.5). In the CARTITUDE-4 as-treated population with standard-risk cytogenetics, 8 PFS events occurred within 1 year and 4 PFS events beyond 1 year of cilta-cel infusion. Twenty-six patients achieved MRD-negative CR at 12 months after cilta-cel; 100.0% of these patients were progression free at 30 months. Fourteen patients were not evaluable for MRD due to: calibration failure (n=12), no sample availability for testing (n=1), or indeterminate results post baseline (n=1).

Conclusions: The PFS rate at 2.5 years for patients with standard-risk RRMM was higher in CARTITUDE-4 compared with CARTITUDE-1, supporting the use of cilta-cel as early as second line in the treatment course. In CARTITUDE-4 (as-treated population), 80.0% of patients with standard-risk cytogenetics were progression free and off treatment at 2.5 years. In patients with standard-risk disease who achieved MRD-negative CR at 1 year, this rate increased to 100.0%. The low rate of progression events in cilta-cel-treated patients with standard-risk cytogenetics shows the profound benefit of a single cilta-cel infusion in this population.

Luciano Costa MD PhD AJO Text

January 14, 2026 Audio Journal of Oncology

Matteo Lambertini MD PhD; San Antonio Breast Cancer Symposium: ALTTO Trial Shows Adjuvant Aromatase Inhibitors Outperform Tamoxifen in Patients with ER-Positive, HER2-Positive Early Breast Cancer

Audio Medica News — Fri, 09 Jan 2026 13:17:30 +0000

Matteo Lambertini MD PhD; San Antonio Breast Cancer Symposium: ALTTO Trial Shows Adjuvant Aromatase Inhibitors Outperform Tamoxifen in Patients with ER-Positive, HER2-Positive Early Breast Cancer

An interview with:

Matteo Lambertini MD PhD, Assistant Professor, University of Genoa, Consultant in Medical Oncology, San Martino IST Hospital, Genoa, Italy.

SAN ANTONIO, USA—Patients with hormone receptor positive HER2-positive early breast cancer had superior outcomes when treated with aromatase inhibitor adjuvant therapy than similar patients treated with adjuvant tamoxifen or other selective estrogen receptor modulators (SERMs). This is the headline finding from a long-term analysis of the large international ALTTO trial reported at the 2025 San Antonio Breast Cancer Symposium by Matteo Lambertini MD PhD, Assistant Professor at the University of Genoa, and Consultant in Medical Oncology, San Martino IST Hospital in Genoa, Italy. After his talk at the conference he discussed the findings with the Audio Journal of Oncology’s Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Matteo Lambertini MD PhD

IN: [GOODWIN] “Matteo Lambertini I am with you here at the San …….. OUT: ……for the Audio Journal of Oncology, I’m Peter Goodwin. 7:05 secs

CONFERENCE DETAILS:

2025 San Antonio Breast Cancer Symposium, San Antonio, Texas USA

ORAL SESSION: GS1-03

“Adjuvant aromatase inhibitor or tamoxifen in patients with hormone receptor-positive/HER2-positive early breast cancer: An exploratory analysis from the ALTTO (BIG 2-06) trial”

SPEAKER:

Matteo Lambertini, University of Genova – IRCCS Ospedale Policlinico San Martino, Genoa, Italy

AUTHORS:

Lambertini1, F. Samy2, E. Agostinetto3, L. Arecco4, P. Freire5, A. Sonnenblick6, G. Arpino7, L. Del Mastro8, A. Choudhury9, N. Harbeck10, I. Vaz-Luis11, V. Kaklamani12, A. Wolff13, A. Partridge14, S. Loi15, S. Fielding16, M. Piccart17, S. Di Cosimo18, E. de Azambuja17;

INSTITUTIONS:

1Medical Oncology, University of Genova – IRCCS Ospedale Policlinico San Martino, Genoa, ITALY, 2Statistics, Frontier Science Scotland, Kingussie, UNITED KINGDOM, 3Oncology, Institut Jules Bordet, Hôpital Universitaire de Bruxelles (H.U.B) and Université Libre de Bruxelles (U.L.B.), Brussels, BELGIUM, 4Oncology, Department of Oncology, Institut Jules Bordet, Hôpital Universitaire de Bruxelles (H.U.B) and Université Libre de Bruxelles (U.L.B.), Brussels, BELGIUM, 5Medical Oncology, Oncologia D’Or Hospital de Câncer de Pernambuco, Recife, BRAZIL, 6Medical Oncology, The Oncology Division, Tel Aviv Sourasky Medical Center, Grey Faculty of Medicine, Tel Aviv University, Tel Aviv, ISRAEL, 7Medical Oncology, Università di Napoli Federico II, Naples, ITALY, 8Medical Oncology, University of Genova – IRCCS Ospedale Policlinico San Martino, Genova, ITALY, 9-, Novartis, Hyderabad, INDIA, 10Oncology, Dept. OB&GYN and CCC Munich, LMU University Hospital, Munich, GERMANY, 11Medical Oncology, Institut Gustave Roussy, Villejuif, FRANCE, 12Medical Oncology, UTH San Antonio, San Antonio, TX, 13Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 14Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 15Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, AUSTRALIA, 16Stat, Frontier Science Scotland, Kingussie, UNITED KINGDOM, 17Medical Oncology, Department of Oncology, Institut Jules Bordet, Hôpital Universitaire de Bruxelles (H.U.B) and Université Libre de Bruxelles (U.L.B.), Brussels, BELGIUM, 18Medical Oncology, Istituto Nazionale dei Tumori (INT), Milano, ITALY.

DISCLOSURES:

Lambertini: Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, Menarini, Nordic Pharma , Roche, Lilly, Novartis, Pfizer, AstraZeneca, Takeda, Ipsen, Sandoz, Libbs, Daiichi Sankyo, Gilead, Menarini, Gilead, Daiichi Sankyo, Roche, Gilead (to the institution).

BACKGROUND:

The optimal adjuvant endocrine therapy (ET) for patients (pts) with hormone receptor-positive (HR+)/HER2-positive (HER2+) early breast cancer (EBC) remains controversial. The present analysis investigated the efficacy of different types of ET in pts with centrally tested HR+/HER2+ EBC treated with modern chemotherapy (CT) and trastuzumab (T)-based regimens at 10-year follow-up.

Patients and methods: ALTTO (BIG 2-06) is an international phase 3 trial in pts with HER2+ EBC randomized to 4 adjuvant anti-HER2 treatments with CT: T alone, lapatinib (L) alone, their sequence (T->L) or their combination (T+L). Pts in the L alone arm, pts with HR-/HER2+ disease and pts with HR+ tumours who did not start adjuvant ET were excluded from the analysis. HER2 and HR status were centrally tested for all pts. Disease-free survival (DFS), time to distant recurrence (TTDR) and overall survival (OS) were compared between pts who received a selective estrogen receptor modulator (SERM) vs. those who received an aromatase inhibitor (AI). To avoid the risk of immortal time bias, pts with HR+/HER2+ disease who switched from one ET to another during the follow-up were excluded. A pre-planned subgroup analysis according to menopausal status at baseline was performed. Among premenopausal women, a comparison was made between SERM alone, SERM + ovarian function suppression (OFS) and AI±OFS (depending on post-CT menopausal status). Multivariable Cox proportional hazards regression models were used to model survival outcomes with adjuvant ET as the predictor. Other covariates in the model were CT timing (concurrent/sequential), tumour grade (G1/2, G3, GX), age (continuous) and tumour size (T, continuous) and a strata variable of axillary lymph node (N0, N1-3, N>=4 nodes, N/A). SERM were used as the reference category for adjusted hazard ratios (aHR).

RESULTS:

This analysis included 2,651 pts with HR+/HER2+ of whom 1,518 (57.3%) received SERM (99.5% tamoxifen) and 1,133 (42.7%) AI. Among 1,259 premenopausal pts, 903 (71.7%) received SERM alone, 238 (18.9%) SERM+OFS and 118 (9.4%) AI±OFS. Median follow-up was 9.9 years (IQR 7.0-10.0 years). Overall, 10-year DFS was 80.1% and 76.5% in the AI and SERM groups, respectively (aHR 0.65; 95% CI 0.52-0.82). Compared to pts treated with SERM, those who received AI had fewer local (0.9% vs. 2.4%) and distant (9.3% vs. 12.1%) recurrences. In subgroup analyses, AI was superior to SERM irrespective of pts (age, menopausal status, body mass index), tumor (T, N, G, HR+ levels, HER2 FISH ratio) and treatment (anti-HER2 arm, CT type and timing) characteristics. In the AI and SERM groups, 10-year TTDR was 85.7% and 83.1% (aHR 0.65; 95% CI 0.50-0.85), and 10-year OS was 88.9% and 89.1% (aHR 0.73; 95% CI 0.53-1.00), respectively. Among premenopausal pts only, 10-year DFS was 90.0%, 77.3% and 77.6% with AI±OFS, SERM+OFS and SERM, respectively (AI±OFS vs. SERM: aHR 0.44; 95% CI 0.23-0.85; SERM+OFS vs. SERM: aHR 0.87; 95% CI 0.61-1.23). In the AI±OFS, SERM+OFS and SERM groups, 10-year TTDR was 92.8%, 82.9% and 85.1% (AI±OFS vs. SERM: aHR 0.57; 95% CI 0.27-1.18; SERM+OFS vs. SERM: aHR 0.94; 95% CI 0.62-1.41), and 10-year OS was 95.6%, 88.7% and 91.3% (AI±OFS vs. SERM: aHR 0.68; 95% CI 0.27-1.73; SERM+OFS vs. SERM: aHR 0.98; 95% CI 0.58-1.66), respectively.

CONCLUSIONS:

In this large 10-year follow-up analysis of pts with centrally tested HR+/HER2+ EBC treated with modern CT+anti-HER2-based therapy in the ALTTO trial, the use of AI was associated with significantly improved DFS and TTDR without differences in OS. The DFS benefit of AI was observed in both premenopausal and postmenopausal pts. These data may help optimizing adjuvant ET choices in pts with HR+/HER2+ EBC and shed light on the need of designing ad hoc clinical trials in this setting.

AJO January 9, 2025: Matteo Lambertini, San Antonio BC Symposium

Jesse Tettero MD PhD; ASH 2025: Measurable Residual Disease Can Predict Overall Survival in Patients with Acute Myeloid Leukemia

Audio Medica News — Thu, 08 Jan 2026 13:38:58 +0000

ASH 2025: Measurable Residual Disease Can Predict Overall Survival in Patients with Acute Myeloid Leukemia

An interview with: Jesse Tettero MD PhD, Amsterdam University Medical Center, Department of Hematology, Amsterdam, Netherlands and: Virginia Tech FBRI Cancer Research Center, Fralin Biomedical Research Institute, Washington, USA.

Reporting from: American Society of Hematology 2025 Annual Meeting, Orlando, USA

ORLANDO, USA—Measurable residual disease (MRD) could soon emerge as a key surrogate endpoint in clinical studies of acute myeloid leukemia indicating overall survival, and speed the introduction of effective new agents. That’s according to findings from the HARMONY Alliance study of European randomized trials reported to the 2025 Annual Meeting of the American Society of Hematology Annual Meeting.

After speaking at the conference, the first author Jesse Tettero, from Amsterdam University Medical Center, Department of Hematology in Amsterdam, Netherlands and Virginia Tech FBRI Cancer Research Center, Fralin Biomedical Research Institute, in Washington, USA, discussed the findings with Audio Journal of Oncology correspondent, Peter Goodwin:

Audio Journal of Oncology with Jesse Tettero MD PhD

IN: [GOODWIN]” I am at the American ….. OUT: …….I’m Peter Goodwin 9:09secs

PUBLICATION: “Blood”, 2025:

Blood (2025) 146 (Supplement 1): 343.

ASH 2025 ABSTRACT Number: 343

LEAD AUTHOR:

Jesse Tettero

Amsterdam University Medical Center, Department of Hematology, Amsterdam, Netherlands and:

Virginia Tech FBRI Cancer Research Center, Fralin Biomedical Research Institute, Washington, United States

TITLE:

Validation of measurable residual disease as a surrogate endpoint in acute myeloid leukemia: A HARMONY Alliance study of European randomized trials

AUTHORS:

Jesse Tettero, Sträng Eric, Sylvie Freeman, Richard Dillon, Jacqueline Cloos, Peter Valk, Konstanze Döhner, Michael Heuser, Christoph Röllig, Christian Thiede, Axel Benner, Luciana Carota, Daniele Dall’Olio, Ana Garcia, Alberto Hernandez Sanchez, Sean Johnson, Soren Lehmann, Javier Martinez Elicegui, Rabea Mecklenbrauck, Klaus Metzeler, Marta Sobas, Ian Thomas, Amin Turki, Laura Tur Gimenez, Brain Huntley, Nigel Russell, Jurjen Versluis, Hartmut Döhner, Jesus Maria Hernandez Rivas, Lars Bullinger, Gert J. Ossenkoppele

ABSTRACT

Introduction: Measurable residual disease (MRD) prior to consolidation therapy is a strong prognostic biomarker for relapse and long-term survival in acute myeloid leukemia (AML). Beyond its prognostic role, MRD is increasingly used to guide therapeutic decisions. A logical next step is regulatory acceptance of MRD as a (co-)primary endpoint in AML, as recently granted by the FDA for MRD in multiple myeloma. However, acceptance in AML is hampered by disease heterogeneity, variability in MRD assessments and a lack of trial-level validation. As MRD-guided treatment becomes more common, future trial outcomes may be confounded by such interventions. Thus, establishing MRD now as a surrogate endpoint is critical to enable accelerated drug approval in AML. Here, we evaluate both individual- and trial-level surrogacy of MRD assessed by multiparameter flow cytometry (MFC) and qPCR for mutant NPM1 using harmonized patient-level data from seven prospective randomized phase II/III trials.

METHODS:

We included patient-level data from 1,858 adult with AML enrolled in trials conducted by AMLSG, HOVON-SAKK, SAL, and UK-NCRI, collected through the HARMONY Alliance. Eligible trials involved randomization to experimental or placebo treatment added to a standard intensive induction chemotherapy, with ≥20 patients per arm and per MRD subgroup. Patients were included if they had a MRD assessment after two chemotherapy cycles by either MFC or qPCR for mutant NPM1. Data were harmonized using the OMOP common data model. Following FDA guidance, we analyzed two levels of surrogacy. For individual-level surrogacy, we examined the association between MRD status and overall survival (OS) using Plackett’s copula models and multivariable Cox regression. For trial-level surrogacy, we quantified the relationship between treatment effects on MRD and OS using hazard ratios (HR) and odds ratios (OR) in weighted least-squares regression. A coefficient of determination (R²) >0.8 with 95% CI lower bound >0.6 was considered strong trial-level surrogacy, consistent with previously accepted surrogate endpoints. Subgroup analyses were conducted by MRD method and transplant status.

RESULTS:

The included trials were AMLSG 09-09 (qPCR MRD assessment), three HOVON-SAKK trials (AML-102, AML-103, AML-132; all MFC), the SAL cohort (qPCR), and the UK-NCRI AML17 trial, which included two separate randomizations (both MFC- and qPCR-MRD).

In multivariable analysis, MRD positivity was associated with significantly worse OS across the cohort (HR: 1.66, 95% CI: 1.33–2.07, p<0.001). This association persisted when stratified by MRD method or treatment arm (placebo vs experimental). The global OR for the association between MRD status and OS was 0.39 (95% CI: 0.32–0.47); among transplanted patients, OR was 0.61 (95% CI: 0.42–0.81), and among non-transplanted patients, 0.33 (95% CI: 0.25–0.41).

Trial-level surrogacy analysis was limited to MFC-based MRD (n= 1,268) due to the limited number of qPCR-based trials. The overall R² between treatment effect on MRD (OR) and OS (HR) was 0.91 (95% CI: 0.56–1.00), suggesting strong surrogacy, though the lower confidence interval bound fell below the predefined threshold. When restricting to non-transplanted patients, R² increased to 0.99 (95% CI: 0.94–1.00), whereas among transplanted patients R² was 0.54 (95% CI: 0.00–1.00), suggesting that transplant may attenuate the association between MRD and OS at the trial level.

CONCLUSIONS:

This pooled analysis represents the largest MRD dataset in AML to date and demonstrates that MRD after induction is a robust individual-level predictor of OS, whether measured by MFC or qPCR for NPM1. MRD retained prognostic value across treatment arms and in multivariable models. These findings reflect strong individual-level surrogacy: MRD-negative patients were more than twice as likely to survive as MRD-positive patients, although this difference was less pronounced in transplanted patients, suggesting that allogeneic transplant may partially mitigate the adverse impact of MRD positivity.

Importantly, trial-level surrogacy was confirmed for MFC-MRD in non-transplanted patients, supporting its use as an intermediate endpoint reasonably likely to predict long-term outcomes in intensively treated AML patients. As MRD-guided therapy and maintenance strategies become standard, this harmonized prospective dataset provides timely evidence to support MRD as a regulatory surrogate endpoint for AML drug development.

Hisham Abdel-Azim MD MS; ASH 2025: Next Generation Sequencing-Assessed Minimum Residual Disease Identifies Young Patients with High-risk/Relapsed B-cell Acute Lymphoblastic Lymphomas Who Can Omit Pre-Transplant Total Body Irradiation

Audio Medica News — Tue, 06 Jan 2026 16:15:10 +0000

Next Generation Sequencing-Assessed Minimum Residual Disease Identifies Young Patients with High-risk/Relapsed B-cell Acute Lymphoblastic Lymphomas Who Can Omit Pre-Transplant Total Body Irradiation

An interview with:

Hisham Abdel-Azim MD MS, Chief, Division of Transplant/Cell Therapy and Hematological Malignancies, Cancer Center, Departments of Pediatrics and Medicine, Loma Linda University School of Medicine, Children Hospital and Medical Center, Loma Linda CA, United States

ORLANDO, Florida—Total body irradiation before allogeneic hematopoietic cell transplantation can be avoided in patients with B-cell lymphomas if you monitor their initial treatment responses by assessing minimum residual disease using next generation sequencing rather than by traditional flow cytometry.

This finding has emerged from the phase two EndRAD trial reported at the 2025 Annual Meeting of the American Society of Hematology by Hisham Abdel-Azim MD MS, Chief, Division of Transplant/Cell Therapy and Hematological Malignancies, Cancer Center, Departments of Pediatrics and Medicine, Loma Linda University School of Medicine, Children Hospital and Medical Center, Loma Linda CA, United States. After his talk at the conference he discussed the findings with the Audio Journal of Oncology’s Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Hisham Abdel-Azim MD MS

IN: [GOODWIN]”I’m reporting now from ……. OUT: …for the Audio Journal of Oncology” 11:12 secs

PUBLICATION:

BLOOD, 2025:

https://ashpublications.org/blood/article/146/Supplement%201/163/553049/High-event-free-EFS-and-overall-survival-OS-after

TITLE:

High event-free (EFS) and overall survival (OS) after non-total body irradiation (TBI) conditioning and allogeneic hematopoietic cell transplantation (HCT) in next-generation-sequencing minimal residual disease (NGS-MRD) negative B-acute lymphoblastic leukemia (B-ALL): Results from the EndRAD trial (PTCTC ONC1701)

AUTHORS

Hisham Abdel-Azim, Troy Quigg, Neena Kapoor, Yueh-Yun Chi, Christine Higham, Amy Keating, Vanessa Fabrizio, Jodi Skiles, Shalini Shenoy, Sajad Khazal, Aliza Gardenswartz, Lisa Madden, Jordan Milner, Rachel Phelan, Emi Caywood, Ulrich Duffner, Jonathan Fish, Jorge Galvez Silva, Alfred Gillio, Rabi Hanna, Jeffrey Huo, Nahal Lalefar, Kris Mahadeo, Kevin McNerney, J. Gregory Dolan, Dana Salzberg, Heather Stefanski, Michael Pulsipher

LEAD INSTITUTION:

Division of Transplant/Cell Therapy and Hematological Malignancies, Cancer Center, Departments of Pediatrics and Medicine, Loma Linda University School of Medicine, Children Hospital and Medical Center, Loma Linda, United States

ABSTRACT

Introduction: HCT is an established curative treatment for children, adolescents, and young adults (CAYA) with high-risk/relapsed B-ALL. Inclusion of TBI in HCT conditioning has been shown to be superior to non-TBI approaches for B-ALL, but is associated with significant late effects. Based upon retrospective data showing low rates of relapse, we hypothesized that patients with negative pre-HCT MRD by next-generation-sequencing of IgH B-cell receptor rearrangements (NGS-MRD) could achieve 2-year EFS exceeding 75% with a non-TBI regimen, an outcome comparable to those receiving TBI-based regimens.

METHODS:

The Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) conducted a phase II prospective trial at 45 centers in North America (ONC1701 EndRAD: NCT03509961) between 2018 and 2025 to evaluate outcomes of myeloablative non-TBI conditioning regimens for allogeneic HCT in B-ALL patients at lower risk for relapse defined by absence of NGS-MRD (Clonoseq) of B-cell receptor rearrangements (BCR) just prior to HCT. Eligibility criteria included age >/= 1 year to <31 years, first or second complete remission status (CR1/CR2), and no isolated or combined CNS disease at relapse. Prior blinatumomab, inotuzumab ozogamicin, or CAR-T treatments were allowed. All graft sources were permitted. Mismatched related/haploidentical grafts received post-transplant cyclophosphamide or TCRαβ/CD19 depletion according to institutional preference. All patients received myeloablative non-TBI conditioning. Graft-versus-host disease (GVHD) prophylaxis was according to graft source and institutional standards.

RESULTS:

Fifty-one patients (51% males) in CR1 (49%) or CR2 (51%) status received HCT. Median age (range) at initial diagnosis and HCT were 11.9 (1.2-28.1) and 13.5 (2.3-32.5) years, respectively. Of patients enrolled, 33% were White/Non-Hispanic, 37% Hispanic, 12% Black or African American, and 18% other. Prior to HCT, 28 patients (55%) received blinatumomab, 1 (2%) received inotuzumab, while 11 (21%) received CAR-T, 7 (14%) received 2 prior immunotherapies, and 4 (8%) had no prior immunotherapy. Forty-four patients (86%) received the preferred study non-TBI conditioning regimen (busulfan, fludarabine, thiotepa); 2 comparable allowed regimens were received: fludarabine, melphalan, and thiotepa by 3 patients (6%) and melphalan, fludarabine, clofarabine, and thiotepa by 4 patients (8%). Donors included HLA matched siblings (41%), mismatched related/haploidentical (33%), matched unrelated (18%), or unrelated cord blood (8%). Related and unrelated donor graft sources were 71% bone marrow and 21% peripheral blood stem cells. Transplant-related mortality in the first 100 days post-HCT was low at 2%. At a median follow up of 2.3 (range: 0.2-6.0) years, the 2-year OS and EFS (alive/relapse-free) were 82% (95% CI: 67.1%, 90.6%) and 76.3% (95% CI: 61.1%, 86.1%), respectively. Five patients (10%) who were pre-HCT NGS-MRD negative by BCR had detectable T-cell receptor sequences (BCR-/TCR+); all 5 are alive and relapse-free. Non-relapse mortality (NRM) was 12% (6 patients, 0.1-2.9 years from HCT to NRM) and occurred predominantly in older children (4 (67%) >/=14 yrs old). Relapses occurred in 6 children, with 4 (67%) undergoing HCT in CR2. Four of the six relapses occurred after matched sibling donor HCT. Acute GVHD occurred in 20 patients (39%, with 15 (75%) grade 1-2 and 5 (25%) grade 3-4). Chronic GVHD occurred in 13 patients (25%) (11 (85%) requiring systemic immunosuppressive treatment).

CONCLUSIONS:

The primary endpoint of our study was met with the 2-year EFS exceeding 75% following non-TBI conditioning and allogeneic HCT in pre-HCT NGS-MRD negative B-ALL. OS in our cohort is comparable to published Center for International Blood & Marrow Transplant Research (CIBMTR) results in B-ALL where patients receive TBI-based conditioning. Our results show that pre-HCT NGS-MRD can be used to allow the choice of myeloablative non-TBI preparative regimens for CAYA undergoing allogeneic HCT that may result in decreased late effects. Additional analyses to be reported at the meeting will more fully investigate factors that impact post-HCT outcomes, including baseline cytogenetics/genomics and post-HCT bone marrow and peripheral blood NGS-MRD, along with planned comparisons to an observational cohort (n=146) enrolled on the trial including infants and older patients treated non-TBI approaches and older children treated with TBI-based regimens.

ASH 2025 Publication Number: 163

Abstract Title :

“High event-free (EFS) and overall survival (OS) after non-total body irradiation (TBI) conditioning and allogeneic hematopoietic cell transplantation (HCT) in next-generation-sequencing minimal residual disease (NGS-MRD) negative B-acute lymphoblastic leukemia (B-ALL): Results from the EndRAD trial (PTCTC ONC1701)”

Aditya Bardia MD MPH; 2025 San Antonio Breast Cancer Symposium: Selective Estrogen Degrader Giredestrant Improves on Standard Endocrine Therapy for Patients with ER-positive, HER2-negative Early Breast Cancer: Phase III lidERA Breast Cancer trial Findings

Audio Medica News — Thu, 18 Dec 2025 13:33:24 +0000

2025 San Antonio Breast Cancer Symposium: Selective Estrogen Degrader Giredestrant Improves on Standard Endocrine Therapy for Patients with ER-positive, HER2-negative Early Breast Cancer: Phase III lidERA Breast Cancer trial Findings

An interview with: Aditya Bardia MD MPH, Professor of Medicine and Director of Translational Research Integration, University of California, Los Angeles and Jonsson Comprehensive Cancer Center, Los Angeles, California USA.

SAN ANTONIO, USA—Significant and clinically meaningful improvements in disease-free survival were reported from the Phase III lidERA Breast Cancer trial at the 2025 San Antonio Breast Cancer Symposium, in San Antonio, USA. First author of the study, Aditya Bardia MD MPH, Professor of Medicine and Director of Translational Research Integration at University of California, Los Angeles and the Jonsson Comprehensive Cancer Center, in Los Angeles, California, met up with Audio Journal Oncology reporter, Peter Goodwin.

Audio Journal of Oncology with: Aditya Bardia MD MPH

IN “[GOODWIN] I am at the San Antonio ……. OUT: …….of Oncology. I’m Peter Goodwin” 7:42 secs

San Antonio Breast Cancer Symposium ABSTRACT: GS1-10

“Giredestrant vs standard-of-care endocrine therapy as adjuvant treatment for patients with estrogen receptor-positive, HER2-negative early breast cancer: Results from the global Phase III lidERA Breast Cancer trial

Speaker:

Aditya Bardia, University of California Los Angeles, Los Angeles, CA

Authors:

Bardia1, P. Schmid2, M. Martín3, S. Hurvitz4, K. Jung5, M. Rimawi6, S. Saji7, G. Werutsky8, N. Harbeck9, S. Loi10, A. Ogiya11, M. Ruiz-Borrego12, A. Alacacıoğlu13, J. Wu14, C. Ye15, M. Liste-Hermoso16, N. Withana16, T. Badovinac Crnjevic17, M. Shah18, P. Pérez-Moreno19, C. Geyer, Jr.20; 1University of California Los Angeles, Los Angeles, CA, 2Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, UNITED KINGDOM, 3Universidad Complutense, GEICAM, CIBERONC, Madrid, SPAIN, 4Department of Medicine, UW Medicine, Fred Hutchinson Cancer Center, Seattle, WA, 5Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, KOREA, REPUBLIC OF, 6Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 7Department of Medical Oncology, Fukushima Medical University, Fukushima, JAPAN, 8Breast Cancer Program, Latin American Cooperative Oncology Group and Centro de Pesquisa em Oncologia, Hospital Sao Lucas PUCRS, Porto Alegre, JAPAN, 9Department of Obstetrics and Gynecology, LMU University Hospital, Munich, GERMANY, 10Division of Cancer Research, Peter MacCallum Cancer Centre and The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, AUSTRALIA, 11Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, JAPAN, 12Breast Cancer Unit, Hospital Universitario Virgen del Rocío, Sevilla, SPAIN, 13Department of Oncology, İzmir Kâtip Çelebi University, Atatürk Training and Research Hospital, İzmir, TURKEY, 14Department of Breast Surgery, Cancer Hospital/Institute, Fudan University, Shanghai, CHINA, 15Department of Oncology Biostatistics, Genentech, Inc., South San Francisco, CA, 16Global Product Development – Clinical Science Oncology (PDOH), F. Hoffmann-La Roche Ltd, Basel, SWITZERLAND, 17PDO – Clinical Science Oncology, F. Hoffmann-La Roche Ltd, Basel, SWITZERLAND, 18Product Development Safety, Genentech, Inc., South San Francisco, CA, 19Product Development Oncology/Hematology (PDOH), Genentech, Inc., South San Francisco, CA, 20Department of Medicine, University of Pittsburgh School of Medicine-UPMC Hillman Cancer Center, Pittsburgh, PA.

Background:

Adjuvant (adj) endocrine therapy (ET) is the mainstay treatment (tx) for estrogen receptor-positive, HER2-negative early breast cancer (ER+ HER2- eBC). However, up to 1/3 of patients (pts) eventually experience recurrence. Clinically, there is an unmet need for more tolerable and efficacious ET to improve adherence and pt outcomes. Giredestrant, a next-generation oral selective estrogen receptor antagonist and degrader (SERD), was shown to be more potent than other SERDs (Liang 2021; Bardia 2023) and demonstrated superior antiproliferative activity vs anastrozole in the neoadj coopERA BC trial (Hurvitz 2023). Results of the prespecified interim analysis of the global, randomized lidERA BC trial (NCT04961996) are presented.

Methods: Pts with Stage I-III ER+ HER2- eBC were randomized 1:1 to giredestrant 30 mg oral daily (with an LHRH agonist in pre- and peri-menopausal women, and men) or standard-of-care ET (tamoxifen or aromatase inhibitor) for 5 years (yr). The primary endpoint was invasive disease-free survival (IDFS). Key secondary endpoints were overall survival (OS), distant recurrence-free interval (DRFI), and safety.

Results: 4170 pts were randomized (Aug 2021-Sep 2023): 2084 to giredestrant; 2086 to standard-of-care ET. Median age was 54.0 yr; 59.3% of pts were postmenopausal; 13.0%, 47.4%, and 39.6% had Stage I, II, and III BC, respectively. Median follow-up at clinical cutoff (Aug 8, 2025) was 32.3 months, with 336 IDFS events. Efficacy is shown in the table. Giredestrant demonstrated superior IDFS vs standard-of-care ET (hazard ratio [HR] 0.70; 95% confidence interval [CI], 0.57, 0.87; p = 0.0014). 3-yr IDFS rates were 92.4% and 89.6%, respectively. There was a trend towards OS improvement in the giredestrant arm vs the standard-of-care ET arm (HR 0.79; 95% CI, 0.56,1.12). The DRFI HR was 0.69 (95% CI, 0.54, 0.89). The most common adverse events (AEs) in the giredestrant vs standard-of-care ET arms, respectively, were arthralgia (48.0% vs 47.1%), hot flush (27.4% vs 28.8%), and headache (15.3% vs 13.2%); the most common Grade 3-4 AEs, hypertension (2.6% vs 2.0%) and arthralgia (1.5% vs 1.8%). Discontinuations due to AEs occurred in 5.3% with giredestrant vs 8.2% with standard-of-care ET.

Conclusions: lidERA BC is the first Phase III trial to demonstrate benefit with an oral SERD in eBC. Giredestrant tx resulted in a statistically significant and clinically meaningful IDFS improvement vs standard-of-care ET in ER+, HER2- eBC. OS trended in favor of the giredestrant arm, and DRFI was improved vs standard-of-care ET. The safety profile was favorable and consistent with known profiles, and the discontinuation rate was slightly lower with giredestrant compared with standard-of-care ET. Overall, the results support giredestrant as a potential new standard for pts with HR+ eBC.

PRESS RELEASE:

Novel Endocrine Therapy Giredestrant Improves Disease-free Survival Over Standard of Care for Patients With Early-stage Breast Cancer in Phase III lidERA Trial

SAN ANTONIO – The investigational, oral selective estrogen receptor degrader (SERD) giredestrant given as an adjuvant therapy showed significant improvement in invasive disease-free survival (iDFS) compared with the current standard-of-care endocrine therapy in patients with early-stage, hormone receptor (HR)-positive, HER2-negative breast cancer, according to the results of the phase III IidERA trial presented at the San Antonio Breast Cancer Symposium (SABCS), held December 9-12, 2025.

“For patients with HR-positive breast cancer—which accounts for about 70% of breast cancer cases— effective adjuvant therapy at the early stage offers a real opportunity to eradicate micrometastatic disease and improve survival in the curative setting,” said presenter Aditya Bardia, MD, MPH, professor of medicine and director of translational research integration at the University of California, Los Angeles Jonsson Comprehensive Cancer Center. “Currently, up to a third of these patients eventually experience recurrence on or after adjuvant endocrine therapy for early breast cancer, and many struggle with tolerating treatment. A more effective, more tolerable treatment option is needed.”

In the global, randomized, open-label, multicenter trial, Bardia and colleagues enrolled patients with HR- positive, HER2-negative breast cancer in stages 1-3 to evaluate the safety and efficacy of giredestrant compared with the current standard-of-care therapies. All patients enrolled had received surgery and, if indicated, completed adjuvant or neoadjuvant chemotherapy. The median age of participants was 54, and 59% were postmenopausal.

In the randomized clinical trial, the researchers assigned 4,170 patients 1:1 to receive either 30 mg of giredestrant or one of four standard-of-care endocrine therapies selected at the discretion of the prescribing physician: tamoxifen, letrozole, anastrozole, or exemestane. Patients received their treatment daily for every 28-day cycle until five years had passed or unacceptable toxicity had occurred.

The researchers assessed patients for the primary endpoint of iDFS, and secondary endpoints included overall survival (OS) and distant recurrence-free interval (DRFI).

The trial met its primary endpoint at a prespecified interim analysis. After a median follow-up of 32.3 months, patients who received giredestrant had significantly better iDFS than their counterparts who received standard-of-care endocrine therapy and were 30% less likely to develop invasive disease progression at the time of follow-up.

The secondary endpoint of DRFI was also met. Patients who received giredestrant were 31% less likely than those in the standard-of-care arm to experience distant recurrence at the time of follow-up.

“Giredestrant demonstrated clinically meaningful superiority to currently well-established standard-of-care endocrine agents: aromatase inhibitors and tamoxifen,” Bardia said. “What is particularly striking and relevant is early separation of curves,” he added, referring to the preliminary OS data. Due to the limited follow-up window, the OS data were immature but showed a positive trend in favor of giredestrant over the standard of care, he explained.

The most common treatment-emergent adverse events (TEAEs) in both the giredestrant and standard-of- care arms were arthralgia, hot flashes, and headache (all of which were primarily low grade and nonnonserious), and the frequency of all of these TEAEs were similar between arms. Grade 3 and 4 TEAEs included hypertension and arthralgia. Few patients died of TEAEs (six and 16 patients died in the giredestrant and standard-of-care arms, respectively), with no treatment-related deaths in the giredestrant arm (one in the standard-of care arm).

Bradycardia—a known class effect of oral SERDs, according to Bardia—was higher in the giredestrant arm at 11.3% than in the standard-of-care arm at 3.2%. The majority were grade 1, asymptomatic, and nonserious, not requiring treatment interruption/discontinuation. Grade 2 adverse events (<1%) were confounded by concurrent conditions/antihypertensives, and all resolved. Treatment discontinuations due to TEAEs were numerically lower in the giredestrant arm at 5.3% than in the standard-of-care endocrine therapy arm at 8.2%.

“For more than a quarter of a century, tamoxifen and aromatase inhibitors have remained the standard endocrine therapy option for patients with early breast cancer,” said Bardia. “Results from lidERA demonstrate clinical superiority of giredestrant to tamoxifen and aromatase inhibitors, placing giredestrant as a new standard in endocrine therapy for patients with early-stage, HR-positive, HER2-negative breast cancer.”

The study’s limitations include limited follow-up and immature OS data.

The study was funded by F. Hoffmann-La Roche Ltd. Bardia has served as a consultant and/or advisory board member to Pfizer, Novartis, Genentech, Merck, Menarini, Gilead Sciences, Alyssum Therapeutics, Vyome, Sanofi, Daiichi Sankyo/AstraZeneca, Bristol Myers Squibb, and Eli Lilly. Bardia has conducted contracted research for or received research grants from Genentech, Novartis, Pfizer, Merck, Sanofi, OnKure Therapeutics, Menarini, Gilead Sciences, Daiichi Sankyo/AstraZeneca, and Eli Lilly.

Daniel J Zheng MD, MHS, MSHP; ASH 2025 Orlando: Childhood Leukemia Cured But Families Broke! “Financial Toxicity” is Often More Worrying than your Child’s Cancer

Audio Medica News — Tue, 16 Dec 2025 21:53:38 +0000

ASH 2025 Orlando: Childhood Leukemia Cured But Families Broke. “Financial Toxicity” is Often More Worrying than you Child’s Cancer

An interview with: Daniel J Zheng MD, MHS, MSHP, Instructor, Children’s Hospital of Philadelphia, Attending Oncologist, Division of Oncology, Philadelphia PA, United States

ORLANDO, USA—Although most children with acute lymphoblastic leukemia can look forward to a cure, their families may face catastrophic financial hardship, according to Daniel Zheng, an Instructor and Attending Oncologist at the Division of Oncology, Children’s Hospital of Philadelphia in Philadelphia, PA, United States. After reporting on the challenge families face of “financial toxicity” from extended curative treatment for ALL Dr. Zheng talked about his findings from the Dana Farber Cancer Institute ALL 16-001 Trial with Audio Journal of Oncology correspondent, Peter Goodwin:

Audio Journal of Oncology: Daniel Zheng

IN: “[GOODWIN] I’m reporting direct … OUT: Oncology, I’m Peter Goodwin 7:38secs

American Society of Hematology 2025 Annual Meeting Abstract 710:

“Cumulative incidence of household material hardship and income loss as measures of financial toxicity during pediatric acute lymphoblastic leukemia (ALL) treatment: A report from the DFCI: ALL 16-001 Trial”

Authors

Daniel Zheng1, Eva Robinson 2, Yael Flamand, 3, Rahela Aziz-Bose 4, Victoria Koch3, Peter Cole5, Lisa Gennarini6, Kelly Getz7, Justine Kahn8, Kristine Karvonen9, Colleen Kelly10, Kara Kelly11, Bruno Michon12, Haley Newman1, Morgan Paul13, Thai Tran14, Puja Umaretiya15, Jennifer Welch16, Edie Weller2, 17, Lewis Silverman8, Kira Bona 10

1 Children’s Hospital of Philadelphia, Division of Oncology, Philadelphia, PA, United States,

2 Boston Children’s Hospital, Biostatistics and Research Design Center, Boston, MA, United States,

3 Dana-Farber Cancer Institute, Boston, MA, United States,

4 Dana-Farber Cancer Institute, Department of Pediatric Oncology, MD, MPH, MA, United States,

5 Rutgers Cancer Institute, New Brunswick, NJ, United States,

6 Montefiore Medical Center, Bronx, NY, United States, 7 University of Pennsylvania, Department of Epidemiology, Philadelphia, PA, United States, 8 Columbia University Irving Medical Center, Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, New York, NY, United States,

9 Seattle Children’s Hospital, Division of Pediatric Hematology-Oncology, Seattle, WA, United States,

10 DanaFarber Cancer Institute, Department of Pediatric Oncology, Boston, MA, United States,

11 Roswell Park Comprehensive Cancer Center, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Department of Pediatrics, Buffalo, NY, United States,

12 Centre Hospitalier Universitaire de Quebec, SaintFoy, QC, Canada,

13 Dana-Farber Cancer Institute, Department of Data Science, Boston, MA, United

States,

14 Charles-Bruneau Cancer Center, CHU Ste-Justine, University of Montreal, Division of Pediatric Hematology-Oncology, Montreal, QC, Canada,

15 UT Southwestern Medical Center, Department of Pediatrics, Dallas, TX, United States,

16 Hasbro Children’s Hospital/Brown University, Division of Pediatric Hematology Oncology, Providence, RI, United States,

17 Harvard Medical School, Department of Pediatrics, Boston, MA, United States

Abstract Body, Introduction:

Over 90% of children with acute lymphoblastic leukemia (ALL) will survive their cancer in the context of >2 years of multi-agent chemotherapy. This intensive treatment paradigm may lead to significant treatment-related financial toxicity for families— an outcome highly relevant to long-term child and family well-being. The magnitude and trajectories of financial toxicity are unknown in pediatric oncology, and necessary to inform optimal screening and intervention strategies for children with cancer and their families. Development of new household material hardship ([HMH], housing, food, or utility insecurity) or income loss during cancer treatment are concrete, targetable metrics of financial toxicity.

We present results from Dana-Farber Cancer Institute (DFCI) ALL Consortium Trial 16-001, the first pediatric oncology clinical trial to systematically collect longitudinal HMH and household income data as an embedded correlative trial aim.

Methods:

DFCI 16-001 (NCT03020030) enrolled children ages 1-<22 years withde novo B- or T-cell ALL at 8 US and Canadian centers from 2017-2021. Participants <18 years were eligible to opt-in to the correlative HMH study at time of initial trial consent. Parents/guardians of participants completed surveys within 32-days of trial enrollment and longitudinally at 6-, 12-, and 24-months. Financial toxicity was the primary endpoint of interest for this secondary analysis, defined by two variables: (1) development of any new HMH domain (food, housing, or utility insecurity) at 6-24 months as compared to baseline and (2) catastrophic income loss defined as ≥25% annual household income loss at 6-24 months compared to baseline. Cumulative incidence of new HMH and catastrophic income loss in the presence of competing risks of coming off study (off-protocol therapy, death, relapse) were estimated using the Aalen-Johansen method. A subcohort analysis was conducted among participants who reported no HMH at baseline. Multivariable competing risk models evaluated the association of patient, household, and disease characteristics with risk of developing new HMH.

Results:

Among 422 participants (15% Hispanic and 7% non-Hispanic Black, 23% single-parent household, 40% annual household income <200% federal poverty level) with evaluable baseline survey data, 115 (27%) reported HMH at baseline. The cumulative incidence of any new HMH was 19.3% (95% CI: 15.9-23.5) at 6-months, 27.7% (95% CI: 23.8-32.4) at 12-months, and 30.0% (95% CI: 25.9-34.7) at 24-months. The cumulative incidence of catastrophic income loss was 20.3% (95% CI: 16.7-24.7) at 6-months, 28.6% (95% CI: 24.5-33.5) at 12-months, and 31.5% (95% CI: 27.2-36.5) at 24-months. Among the subcohort of 307 families with no baseline HMH, the cumulative incidences of any new HMH or catastrophic income loss at 24-months were 24.3% (95% CI: 19.9-29.6) and 27.9% (95% CI: 23.1-33.7), respectively. In multivariable modeling, children who identified as non-Hispanic Black (RR 3.5, 95% CI: 1.7-7.3), lived in a single-parent household (RR 2.1, 95% CI: 1.3-3.2), preferred a non-dominant language (i.e. non-English for US participants and non-English/French for Canadian participants, RR 2.1, 95% CI: 1.2-3.6), or had baseline household income <200% federal poverty level (RR 1.8, 95% CI: 1.1-2.9) were more likely to develop new HMH during treatment.

Conclusion:

Nearly a third of families of children receiving chemotherapy for ALL develop catastrophic financial toxicity during therapy including new unmet basic needs such as food insecurity, or ≥25% income loss. A majority experience this financial toxicity by 6-months into treatment, identifying a key inflection point for potential intervention. Importantly, nearly 1 in 4 families who had no HMH at the time of their child’s diagnosis developed HMH during therapy. These findings stress the clinical importance of longitudinal financial screening over the course of cancer treatment, given the high prevalence of new material needs that arise and the potential to address these needs with family-centered interventions. Future work will assess the impact of early financial toxicity on clinical outcomes in this population and focus on the development of interventions to mitigate the profound financial toxicity impacting families during leukemia care.

Keywords:

Clinical Trials, Lymphoid Malignancies, Supportive Care, Human, Study Population, Health Disparities Research, Lymphoid Leukemias, Health Economics, Patient-Reported Outcomes, Diseases, Clinical Research, ALL, Research, Treatment Considerations, Pediatric, Clinical Practice (Health Services And Quality)

Peihua Lu MD and Robert Chiesa MD PhD; ASH 2025, Orlando: Dramatic Remissions with “Off-the-Shelf” and “Base Edited” CAR T-cell Therapies in Children with Relapsed/Refractory T-Cell Malignancies

Audio Medica News — Fri, 12 Dec 2025 20:04:41 +0000

https://www.audiomedica.com/wp-content/2025/12/251209-0900-Peihua-Lu-Robert-Chiesa-C2998-Discussion-at-ASH-AJO-PRODUCTION-MASTER.mp3Dramatic Remissions with “Off-the-Shelf” and “Base Edited” CAR T-cell Therapies in Children with Relapsed/Refractory T-Cell Malignancies

A discussion interview with Peihua Lu MD from Lu Daopei Hospital in Beijing, China and Robert Chiesa MD PhD from Great Ormond Street Hospital for Children, London, UK, at the American Society of Hematology Annual Meeting in Orlando, Florida, USA

ORLANDO, USA—Children and young adults whose T-cell malignancies had become refractory to all standard treatments have been rescued by means of two different chimeric antigen receptor T-cell therapies: one developed commercially in China and the other created in the laboratory of a leading children’s hospital in London by means of a new method of engineering DNA called: “base editing”.

At the 2025 American Society of Hematology annual meeting in Orlando, Florida, lead author of the Chinese study, Peihua Lu MD from Lu Daopei Hospital in Beijing and team-leader Robert Chiesa MD PhD from Great Ormond Street Hospital for Children, London, UK, met up with Audio Journal of Oncology anchor, Peter Goodwin, to discuss their pioneering early studies which seem to offer hope for patients and their families.

Audio Journal of Oncology: Peihua Lu MD and Robert Chiesa MD PhD

IN: “[GOODWIN] Welcome to…. OUT: ……..from all of us, Good-bye ” 33:51

A discussion on ASH ABSTRACTS at the 2025 Annual Meeting:

Abstract 1042: “CTD402, allogeneic anti-CD7 CAR t-cell, in relapsed or refractory (R/R) t-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) – report of clinical outcomes at the recommended phase 2 dose (RP2D)”

Abstract 1041: “Universal base-edited CAR7 T cells for T-cell acute lymphoblastic leukemia”

Jeanne Tie MD, ESMO Berlin: Liquid Biopsy Brings Chemo-free Option for Patients with Stage Three Colon Cancer

Audio Medica News — Mon, 01 Dec 2025 12:38:49 +0000

An interview with Jeanne Tie MD, Medical Oncologist, Peter MacCallum Cancer Centre and Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

BERLIN, Germany—Liquid biopsy as a means of monitoring disease control in patients with stage three colon cancer has been investigated in a study from Melbourne, Australia reported to the 2025 Annual Congress of the European Society for Medical Oncology, ESMO. The aim was to discover whether patients with ctDNA negative biopsy findings could safely avoid chemotherapy and be spared toxicities including neuropathy.

After reporting findings from the AGITG DYNAMIC-III trial, lead author Jeanne Tie MD, who is a Medical Oncologist at the Peter MacCallum Cancer Centre in Melbourne, Australia, discussed the results with the Audio Journal of Oncology’s reporter, Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY with：Jeanne Tie MD. IN: “[GOODWIN] I am at the European Society for ….. OUT: …..Audio Journal of Oncology, I’m Peter Goodwin. 10:20 sec

ESMO 2025 ABSTRACT LBA9 (Presidential Symposium):

“ctDNA-guided adjuvant chemotherapy de-escalation in stage III colon cancer: Primary analysis of the ctDNA-negative cohort from the randomized AGITG DYNAMIC-III trial (Intergroup study of AGITG and CCTG)”

Speaker:

Jeanne Tie (Melbourne, Australia, VIC)

Authors:

Jeanne Tie (Melbourne, Australia, VIC) Yuxuan Wang (Baltimore, United States of America) Jonathan M. Loree (Vancouver, Canada) Joshua Cohen (Baltimore, United States of America) David Espinoza (Camperdown, Australia) Rachel Wong (Box Hill, Australia) Timothy J. Price (Woodville, Australia) Niall Tebbutt (Heidelberg, Australia) Matthew Burge (Herston, Australia) James Lynam (Waratah, Australia) Belinda Lee (Melbourne, Australia) Samuel J. Harris (Bendigo, Australia) Lorraine Chantrill (Wollongong, Australia) Daniel A. Breadner (London, Canada) Christopher O’Callaghan (Kingston, Canada) Chetan Bettegowda (Baltimore, United States of America) Nicholas Papadopoulos (Baltimore, United States of America) Kenneth Kinzler (Baltimore, United States of America) Bert Vogelstein (Baltimore, United States of America) Peter Gibbs (Parkville, Australia)

Background

Adjuvant chemotherapy (ACT) benefit is uncertain for any individual patient (pt). Post-surgery circulating tumour DNA (ctDNA) testing could support risk-adjusted treatment selection. The DYNAMIC-III study explored ACT de-escalation or escalation, informed by post-surgery ctDNA results.

Methods

In this multicentre, randomised, phase II/III trial, pts with stage III colon cancer underwent tumour-informed ctDNA testing 5-6 weeks post-surgery and were randomised (1:1) to ctDNA-guided or standard management. Clinicians pre-specified standard ACT. In the ctDNA-guided arm, ctDNA-negative results prompted ACT de-escalation: from 6 to 3 months of fluoropyrimidine (FP) or observation, from 3 months of doublet to single-agent FP, or from 6 months of doublet to 3 months doublet or single-agent FP. The primary endpoint was 3-year recurrence-free survival (RFS). A sample size of 750 provided 80% power with a one-sided 97.5% CI to demonstrate non-inferiority (NI) with a NI margin of 7.5%.

Results

Of 968 evaluable pts, 702 (72.5%) were ctDNA-negative; 353 assigned to ctDNA-guided and 349 to standard management. Median follow-up was 45 months. 319 (90.4%) pts received ctDNA-guided per-protocol de-escalation. Treatment de-escalation reduced oxaliplatin-based chemotherapy use versus standard management (34.8% vs 88.6%, P < 0.001) and lowered grade 3+ adverse events of special interest (6.2% vs 10.6%, P = 0.037) and treatment-related hospitalisation (8.5% vs 13.2%, P = 0.048). However, non-inferiority of ctDNA-guided de-escalation was not confirmed (3-year RFS, 85.3% vs 88.1%; difference = -2.8%; 97.5% lower CI = -8.0%). Pre-planned subgroup analysis suggested de-escalation may be non-inferior in clinical low-risk (T1-3N1) tumours (3-year RFS, 91.0% vs. 93.2%; difference = -2.2%; 97.5% lower CI = -7.2%).

Conclusions

Stage III colon cancer pts with negative post-surgery ctDNA had low recurrence risk. ctDNA-guided de-escalation is feasible, substantially reduces oxaliplatin exposure and adverse events, with outcomes approaching standard management, especially for clinical low-risk tumours.

Clinical trial identification

ACTRN12617001566325 Date registered: 21 November 2017.

Legal entity responsible for the study

Australasian GastroIntestinal Trials Group (AGITG).

Funding

Marcus Foundation, NHMRC, Virginia and Ludwig Fund for Cancer Research, Lustgarten Foundation, Conrad R Hilton Foundation, Sol Goldman Charitable Trust, NIH, Eastern Health Research Foundation (Zouki Research Grant), Canadian Cancer Society, Canadian Institutes of Health Research (CIHR).

Paul H Cottu MD PhD, ESMO Berlin: Chemo-Free Regimen with Neoadjuvant CDK 4/6 Inhibition plus Endocrine Therapy Benefits Patients with High-Risk ER+ HER2- Early Breast Cancer

Audio Medica News — Mon, 24 Nov 2025 21:46:55 +0000

Chemo-Free Regimen with Neoadjuvant CDK 4/6 Inhibition plus Endocrine Therapy Benefits Patients with High-Risk ER+ HER2- Early Breast Cancer

An interview with: Paul H Cottu MD PhD, Medical Oncologist and Associate Professor, Institute Curie, Paris, France

BERLIN, Germany—Patients with high-risk, hormone receptor positive, HER2 negative early breast cancers, who would typically be candidates for chemotherapy, had good clinical responses, high biological responses and good rates of surgery in a clinical trial using a chemotherapy-free neoadjuvant regimen consisting of letrozole hormone therapy plus abemaciclib CDK 4/6 inhibition.

Medical Oncologist Paul Cottu MD PhD from the Institute Curie in Paris, France, reported findings from RIBOLARIS trial at the 2025 Annual Congress of the European Society for Medical Oncology held in Berlin. At his poster during the conference he talked about the study findings with Audio Journal of Oncology reporter Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY Paul H Cottu MD PhD

IN: “[GOODWIN] I am at the European ….. OUT: …I’m Peter Goodwin 7:56secs

ESMO ABTRACT 296O:

“Risk of recurrence (ROR) after neoadjuvant ribociclib plus ET in clinically high-risk ER+/HER2− BC: Preliminary analysis of the SOLTI-RIBOLARIS trial”

Speaker: Paul H. Cottu (Paris, France)

Authors:

Paul H. Cottu (Paris, France) Aleix Prat (Barcelona, Spain) Tomás Pascual (Barcelona, Spain) Huilin Hu (East Hanover, United States of America) Estelle Roux (Basel, Switzerland, NJ) Francisco Javier Salvador Bofill (Seville, Spain) Joana M. Ribeiro (Villejuif, France) Isabel Blancas López-Barajas (Granada, Spain) Thomas Bachelot (Lyon, France) Jerome Lemonnier (Paris, France) Juan M. Ferrero-Cafiero (Barcelona, Spain) Pablo Tolosa Ortega (Madrid, Spain, Valencia) Antonio Mulero-Sánchez (Barcelona, Spain) Thayane Antoniolli Crestani (Brussels, Belgium) Roisin M. Connolly (Cork, Ireland, MD) Cynthia X. Ma (St. Louis, United States of America) Antonio C. Wolff (Baltimore, United States of America, MD) Guillermo Villacampa (Barcelona, Spain) Thibault De La Motte Rouge (Rennes, France) Joaquín Gavilá-Gregori (Valencia, Spain)

Background

The CDK4/6 inhibitors (CDK46/i) are approved for early-stage HR+/HER2− breast cancer (BC). The randomized neoadjuvant NeoPAL and CORALLEEN trials provided proof of concept that CDK4/6i in combination with endocrine therapy (ET) have similar activity to multi-agent chemotherapy in pts with luminal B-PAM50 based- BC subtype. The PAM50-derived ROR score was identified as an endpoint of interest after neoadjuvant CDK4/6i-ET. The RIBOLARIS trial was designed to evaluate whether pts with ROR-low disease following neoadjuvant ribociclib (RIB) and ET can safely omit adjuvant chemotherapy.

Methods

RIBOLARIS is an open-label, single-arm, multicenter trial in pts with primary operable stage II, grade 2/3, Ki67 ≥20%, HR+/HER2− BC who are candidates for adjuvant chemotherapy. The study evaluates safety and long-term efficacy of a non-chemo regimen (RIB-ET) in pts with tumors showing a ROR-low score after 6 neoadjuvant cycles of RIB-ET (600 mg/day 3 weeks ON/1 week OFF + ET: letrozol 2.5 mg/day) followed by surgery (within 10 days). Pts with ROR-med/high tumors will receive chemotherapy-based treatment followed by RIB-ET. This preplanned Interim Analysis analyzed safety and efficacy after 686 surgeries. We expected at least 40% of the pts to achieve a ROR-low score after neoadjuvant RIB-ET.

Results

Among the enrolled pts, baseline characteristics included: median age 57 (38-84), postmenopausal status 62%, tumor stage IIA 60%, node-negative 60%, and histological grade 2 74%. At data cut-off, 686 out of 1100 surgeries (62.4%) were performed. Interestingly, we observed that 361 pts (52.6%) achieved a ROR-low score (Mean 11.3, 95% CI 10.5-12.2), while 325 pts (47.4%) had a med/high ROR score (Mean 36.9, 95% CI 34.2-39.5). The most common grade 3-4 severity TEAEs were neutropenia (grade 3: 46.3%; grade 4: 3.5%) and transaminases increased (grade 3: 10.4%; grade 4: 1.5%).

Conclusions

These preliminary results from the RIBOLARIS trial confirm and extend the findings from CORALLEEN and NeoPAL trials, demonstrating that a subset of pts with early-stage HR+/HER2− BC achieve ROR-low disease after neoadjuvant RIB-ET and may be candidate to spare chemotherapy. There was no new safety signal.

Clinical trial identification

NCT05296746.

Li Zhang MD; ESMO 2025: Patients with EGFR-mutated Lung Cancer Progressing After Tyrosine Kinase Therapy Live Longer with Sacituzumab Tirumotecan Therapy

Audio Medica News — Wed, 19 Nov 2025 12:53:36 +0000

An interview with Li Zhang MD, Medical Oncologist and Full Professor, Sun Yat-sen University Cancer Center, Guangzhou, China

BERLIN, Germany—A doubling of progression-free survival, and highly statistically significant benefit for overall survival, has been achieved in patients with epidermal growth factor- (EGFR-) mutated non-small cell lung cancers that had become refractory to EGFR tyrosine kinase inhibitor therapy in a study in which treatment with the antibody drug conjugate (ADC) sacituzumab tirumotecan was compared with standard platinum-based chemotherapy.

At the 2025 Annual Congress of the European Society for Medical Oncology (ESMO) Professor Li Zhang MD, a medical oncologist and full professor at Sun Yat-sen University Cancer Center in Guangzhou, China, reported findings from the randomized, multi-center phase III OptiTROP-Lung04 study at a late-breaking session. After his talk he discussed the findings with Audio Journal of Oncology reporter, Peter Goodwin:

AUDIO JOURNAL OF ONCLOGY: Li Zhang MD

IN: “[GOODWIN] I’m here at ……OUT: …..I’m Peter Goodwin 8:42 secs

ESMO ABSTRACT LBA5:

Sacituzumab tirumotecan (sac-TMT) vs platinum-based chemotherapy in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) following progression on EGFR-TKIs: results from the randomized, multi-center phase III OptiTROP-Lung04 study

Speaker:

Li Zhang (Guangzhou, China)

Authors:

Li Zhang (Guangzhou, China) Wen Feng Fang (Guangzhou, China) Lin Wu (Changsha, China) Xiangjiao Meng (Jinan, China) Yu Yao (Xi’an, Shaanxi Province, China) Wei Zuo (Nanchang, China) Wenxiu Yao (Chengdu, China) Yanyan Xie (Nanning, China) Yu Zhang (Mianyang, China) Jiuwei Cui (Changchun, China) Yongchang Zhang (Changsha, China) Xingya Li (Zhengzhou, China) Wu Zhuang (Fuzhou, China) Jian Fang (Beijing, China) Qiming Wang (Zhengzhou, China) Wei Jiang (Nanning, China) Kai Li (Tianjin, China) Yina Diao (Chengdu, China) Junyou Ge (CHENGDU, China) Yunpeng Yang (Guangzhou, China)

Background

Sac-TMT is a TROP2 ADC developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor. Sac-TMT demonstrated significant survival benefits over docetaxel in EGFRm NSCLC after failure of EGFR-TKI and platinum-based chemotherapy (Fang et al., BMJ 2025). Here, we first report the final PFS analysis and preplanned interim OS analysis results from the phase 3 OptiTROP-Lung04 study (NCT05870319).

Methods

Patients (pts) were randomized (1:1) to receive sac-TMT monotherapy (5 mg/kg Q2W) or chemotherapy (pemetrexed 500 mg/m2 + carboplatin AUC 5 or cisplatin 75 mg/m2 Q3W for 4 cycles followed by maintenance of pemetrexed). The primary endpoint was PFS assessed by blinded independent review committee (BIRC) with OS as a key secondary endpoint tested hierarchically.

Results

A total of 376 pts (median age 59.5 yrs; 39.6% male; 79.3% ECOG PS 1; 94.7% prior 3rd-generation EGFR TKI) were randomized to the sac-TMT (n=188) or chemotherapy (n=188) groups. At a median follow-up of 18.9 mo, 21.3% of pts (sac-TMT) vs 1.6% (chemotherapy) remained on treatment. Sac-TMT demonstrated highly statistically significant and clinically meaningful improvements in PFS and OS compared to chemotherapy (Table). Grade ≥ 3 TRAEs occurred in 49.5% and 52.2%, and TRSAEs in 7.4% and 17.0% of pts in sac-TMT and chemotherapy arms, respectively. No drug-related interstitial lung disease/pneumonitis occurred in either arm.

Sac-TMT (n=188) Chemotherapy (n=188)

Median PFS (BIRC), mo (95% CI) 8.3 (6.7 – 9.9) 4.3 (4.2 – 5.5)

HR (95% CI) 0.49 (0.39 – 0.62)

P-value <0.0001

12-mo PFS rate, %, (95% CI) 32.3 (25.5 – 39.2) 7.9 (4.4 – 12.8)

Median OS, mo (95% CI) NR (21.5 – NE) 17.4 (15.7 – 20.4)

HR (95% CI) 0.60 (0.44 – 0.82)

P-value 0.0006

Adjusted median OS*, mo (95% CI) NR (21.5 – NE) 17.2 (15.4 – 18.9)

HR (95% CI) 0.56 (0.41 – 0.77)

P-value 0.0002

ORR (BIRC), % (95% CI) 60.6 (53.3, 67.7) 43.1 (35.9, 50.5)

Median DOR (BIRC), mo (95% CI) 8.3 (6.2 – 10.0) 4.2 (3.0 – 4.4)

Data cutoff: Jul 06, 2025. P-value was presented as one-sided. *censored at the date of initiation of subsequent anti-tumor ADC drug therapy.

Conclusions

Sac-TMT is the first TROP2 ADC to significantly improve PFS and OS over platinum-based chemotherapy, with manageable safety in EGFR-TKI resistant NSCLC, positioning it as a potential new standard of care for this population.

Clinical trial identification

NCT05870319.

Legal entity responsible for the study

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Erwei Song MD PhD, ESMO Berlin: Antibody Drug Conjugate Trastuzumab Resetecan Brings Early Significant Progression Free Survival Benefit in Patients with Previously Treated HER2+ Advanced Breast Cancer

Audio Medica News — Fri, 14 Nov 2025 15:06:19 +0000

An interview with: https://www.audiomedica.com/wp-content/2025/11/251019-Erwei-Song-ESMO-2025-PRODUCTION-MASTER.mp3, Director of Health Science Center, President, Sun Yat-sen Memorial Hospital, Guangzhou (SYSU), Guangzhou, China.

BERLIN, Germany—The open-label HORIZON-Breast01 phase-three study has reported early data showing that, for previously treated patients with advanced or metastatic breast cancer, progression-free survival improved from a median of 8.3 months with pyrotinib plus capecitabine standard of care to 30.6 months among patients in the experimental arm who received monotherapy with the new antibody drug conjugate (ADC) trastuzumab resetecan. Furthermore, the ADC had a favorable safety profile with low occurrence of interstitial lung disease (ILD).

Findings were reported at the 2025 Annual Congress of the European Society for Medical Oncology by Erwei Song MD PhD, Director of the Health Science Center, President, Sun Yat-sen Memorial Hospital, Guangzhou (SYSU), in Guangzhou, China. After his talk at the conference, Professor Song discussed the findings with Audio Journal of Oncology reporter Peter Goodwin:

Audio Journal of Oncology: Erwei Song MD PhD

IN: “[GOODWIN] I am at …… OUT: …….of Oncology, I’m Peter Goodwin. 7:42secs

ESMO ABSTRACT LBA19:

“SHR-A1811 versus pyrotinib plus capecitabine in human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic breast cancer (BC): A multicenter, open-label, randomized, phase III study (HORIZON-Breast01)”

Speaker: Erwei Song (Guangzhou, China)

Authors:

Erwei Song (Guangzhou, China) Herui Yao (Guangzhou, China) Huiping Li (Beijing, China) Yongmei Yin (Nanjing, China) Qing Yuan Zhang (Harbin, China) Shusen Wang (Guangzhou, China) Quchang Ouyang (Changsha, China) Tao Sun (Shenyang, Liaoning, China) Xiaojia Wang (Hangzhou, China) Weimin Xie (Nanning, China) Biyun Wang (Shanghai, China) Wei Li (Changchun, China) Min Yan (Zhengzhou, China) Cuizhi Geng (Shijiazhuang, China) Yuan Peng (Beijing, China) Yaping Yang (Guangzhou, China) Fangli Dong (Shanghai, China) Ying Zhang (Shanghai, China) Lin Cheng (Shanghai, China) Xiaoyu Zhu (Shanghai, China)

Background

SHR-A1811, a HER2-targeted antibody-drug conjugate, proved substantial single agent antitumor activity in heavily pretreated solid tumors as shown in a global phase 1 trial (J Clin Oncol. 2024). Here, we first report the interim analysis of SHR-A1811 versus pyrotinib plus capecitabine in HER2+ advanced/metastatic BC from the pivotal phase 3 HORIZON-Breast01 study.

Methods

Taxane- and trastuzumab-pretreated patients (pts) with HER2+ advanced/metastatic BC were randomized (1:1) to receive intravenous SHR-A1811 or oral pyrotinib plus capecitabine. The primary endpoint was PFS by blinded independent central review (BICR).

Results

As of Jun 30, 2025, 287 pts were randomized (SHR-A1811, n=142; pyrotinib plus capecitabine, n=145; IHC 3+: 76.1% vs. 71.7%; HR+: 47.9% vs. 47.6%; median lines of prior systemic treatments: 1 vs.1; prior pertuzumab: 71.8% vs. 72.4%), with median follow-up of 15.9 months (95% CI 14.6–17.1) for SHR-A1811, and 15.3 months (95% CI 14.3–16.6) for pyrotinib plus capecitabine. The PFS by BICR was significantly improved in the SHR-A1811 group than in the pyrotinib plus capecitabine group (30.6 months vs. 8.3 months; HR 0.22 [95% CI 0.15–0.34]; p<0.0001; table). Although the median OS was not yet reached, SHR-A1811 showed a clear OS benefit trend. Median treatment duration was 19.5 months (95% CI 17.3–NR) with SHR-A1811, 7.1 months (95% CI 5.6–9.2) with pyrotinib, and 7.5 months (95% CI 5.7–9.6) with capecitabine. Similar rates of TRAEs were observed. Interstitial lung disease (ILD) occurred only in 4 pts (2.8%) receiving SHR-A1811 (grade 1/2: 3 [2.1%]; grade 3: 1 [0.7%]).

Conclusions

SHR-A1811 exhibited significant PFS benefit and strong trend in OS benefit versus pyrotinib plus capecitabine in the second-line therapy in HER2+ advanced/metastatic BC, with favorable safety profile of low ILD occurrence.

Clinical trial identification

NCT05424835.

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

Dong, Y. Zhang, L. Cheng, X. Zhu: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Andrew Clamp MD, PhD, ESMO Berlin: Weekly Dose-Dose Chemotherapy Brings Big Survival Benefit for Patients with High-Risk Ovarian Cancer

Audio Medica News — Wed, 12 Nov 2025 14:10:26 +0000

An interview with: Andrew Clamp MD, PhD, Consultant Medical Oncologist, Christie Hospital, Manchester, UK

BERLIN, Germany—An important therapeutic gain in terms of overall- and progression-free survival has been achieved merely by changing the chemotherapy dose schedule given to patients with high-risk stage three or four epithelial ovarian cancer.

This was reported from the ICON8B: GCIG phase-three randomised trial by Andrew Clamp MD PhD of the Christie Hospital in Manchester, England, at the 2025 Annual Congress of the European Society for Medical Oncology. Dr. Clamp discussed the findings with our reporter, Peter Goodwin.

Audio Journal of Oncology interview: Andrew Clamp MD, PhD

IN: “[GOODWIN] I’m at the European ….. OUT: ….Journal of Oncology, I’m Peter Goodwin” 7:21secs

https://www.annalsofoncology.org/article/S0923-7534(25)02624-9/pdf

ESMO ABSTRACT:

1064O – ICON8B: GCIG phase III randomised trial comparing first-line weekly dose-dense chemotherapy + bevacizumab to three-weekly chemotherapy + bevacizumab in high-risk stage III-IV epithelial ovarian cancer (EOC): Final overall survival (OS) analysis

Speaker: Andrew R. Clamp (Manchester, United Kingdom)

Authors: Andrew R. Clamp (Manchester, United Kingdom) Iain McNeish (London, United Kingdom) Domenico Radice (London, United Kingdom) Rosemary Lord (Liverpool, United Kingdom) Agnieszka Michael (Guildford, United Kingdom, Surrey) Audrey Cook (Cheltenham, United Kingdom) Roshan Agarwal (Northampton, United Kingdom, Northamptonshire) Axel Walther (Bristol, United Kingdom) Sarah P. Blagden (Oxford, United Kingdom) Dearbhaile O’Donnell (Dublin, Ireland) James D. Brenton (Cambridge, United Kingdom) Sudha Sundar (Birmingham, United Kingdom) Cristiana Sessa (Bellinzona, Switzerland) Laura R. Murphy (London, United Kingdom) Francesca Schiavone (London, United Kingdom) Aleksandra Gentry-Maharaj (London, United Kingdom) Richard S. Kaplan (London, United Kingdom) Mahesh K. Parmar (London, United Kingdom, London) Jonathan A. Ledermann (London, United Kingdom)

ESMO Abstract

Background

In ICON8B the use of dose-dense weekly paclitaxel (ddwT) with 3-weekly (q3w) carboplatin (C) and bevacizumab (BEV) as first-line treatment improved median progression-free survival (PFS) by 5.5 months (m) compared to standard q3w paclitaxel (T) dosing with C+BEV (22.2m vs 16.7m; Hazard Ratio (HR) 0.75, 95% CI 0.62-0.90 p=0.002). We now report the final OS analysis conducted at trial closure.

Methods

Eligible participants (pts) with high-risk stage III (residual disease >1cm diameter after immediate primary surgery (IPS) or requirement for primary chemotherapy) or stage IV EOC were randomised 1:1:1 to Arm B1 (standard- q3w C AUC5/6+q3w T 175mg/m2+ q3w BEV 7.5mg/kg); Arm B2- (q3w C AUC5/6+ddwT 80mg/m2); Arm B3- (q3w C AUC5/6+ddwT 80mg/m2+ q3w BEV 7.5mg/kg). Up to six cycles chemotherapy and 18 BEV cycles were administered. Arm B2 recruitment discontinued after ICON8 saw no evidence of PFS improvement with q3wCddwT vs q3wCT. OS was a key secondary outcome and pts were followed for survival endpoints until trial closure on 18th Dec 2024 at end of academic funding.

Results

From 07/2015 to 03/2020 579 pts were randomised to arms B1 + B3. Median age was 64 years; 91% had High Grade Serous Carcinoma; 93% Stage IIIc/IV; 84% primary chemotherapy with planned delayed primary surgery, 14% IPS, 2% inoperable; 50.2% cases sequenced for germline BRCA1/2 mutations. After a median follow-up of 72.0m, 411 deaths were reported (197 in B3; 214 in B1). Median OS was 49.8m (95% CI 43·7-54.5m) in B3 and 39.6m (95% CI 34·7-45·0m) in B1 (HR 0·79, 95% CI 0·65-0·95, p=0·010). In pts receiving primary chemotherapy, median OS was 47.3m (95% CI 42.0-52.6m) in B3 and 37.1m (95% CI 32.3-42.1m) in B1.

Conclusions

In pts with high-risk stage III-IV EOC, the use of ddwT in combination with q3w C + BEV as first-line systemic therapy improves median OS by 10.2m compared to q3w T dosing. ddwT with q3wC+BEV should now be considered a standard-of-care first-line treatment option in this group. Further research is required to determine whether efficacy of this regimen is impacted by tumour homologous recombination deficiency and intrinsic chemosensitivity.

Clinical trial identification

ISRCTN10356387.

Legal entity responsible for the study

University College London.

Funding

Cancer Research UK and Medical Research Council.

Nima Nabavizadeh MD; ESMO Berlin: Multi-Cancer Early Detection Test: PATHFINDER II study Finds Early Promise

Audio Medica News — Fri, 07 Nov 2025 13:57:38 +0000

An interview with Nima Nabavizadeh MD, Associate Professor of Radiation Medicine, Oregon Health & Science University (OHSU), Portland, USA, Chief Medical Officer, Cancer Early Detection Research Center, Portland, Oregon.https://www.audiomedica.com/wp-content/2025/11/251107-Nima-Nabavizadeh-MD-ESMO-2024-PRODUCTION-MASTER.mp3

BERLIN, Germany—A pan-cancer early detection test, that identifies “methylation fingerprints” for a wide range of cancers, has been shown to find more cancers sooner than conventional screening according to research reported to the European Society for Medical Oncology (ESMO) 2025 Annual Congress.

Nima Nabavizadeh MD, Associate Professor of Radiation Medicine at the Oregon Health & Science University (OHSU) in Portland, USA, who is also Chief Medical Officer of the Cancer Early Detection Research Center in Portland, Oregon gave a report on the safety and performance of the test at the ESMO congress. Afterwards he spoke with our reporter, Peter Goodwin:

Audio Journal of Oncology: Nima Nabavizadeh MD

IN: “[GOODWIN]I am at the ESMO meeting …. OUT: ……of oncology. I’m Peter Goodwin” 9:55sec

ESMO ABSTRACT LBA64:

Safety and performance of a multi-cancer early detection (MCED) test in an intended-use population: Initial results from the registrational PATHFINDER II study

https://assets.grail.com/wp-content/uploads/2025/10/ESMO-2025_PF2-Initial-Results_Presentation_FINAL-CLEAN-10.16.2025.pdf

Speaker:

Nima Nabavizadeh (Portland, United States of America)

Authors:

Nima Nabavizadeh (Portland, United States of America) Charles McDonnell III (Sacramento, United States of America) Dax Kurbegov (Nashville, United States of America) Marc Matrana (New Orleans, United States of America) Shirish Gadgeel (Detroit, United States of America) Raymond H. Kim (Toronto, Canada) Gretchen Stipec (Fountain Valley, United States of America) Kevin Oeffinger (Durham, United States of America) Michael J. Demeure (Newport Beach, United States of America) Roland Matthews (Atlanta, United States of America) Rebecca Kaltman (Fairfax, United States of America) Tamar Toronjadze (Flushing, United States of America) Cora N. Sternberg (New York, United States of America) Jennifer Tran (Washington, United States of America) Natalia Colocci (Mountain View, United States of America) Leonardo Forero (Amarillo, United States of America) Margarita Lopatin (Menlo Park, United States of America) Margaret McCusker (Menlo Park, United States of America) Karthik Giridhar (Rochester, United States of America)

Background

The MCED test (Galleri®) detects cancer signals from cell-free DNA in blood and predicts cancer signal origin (CSO) to guide diagnostic (dx) evaluation. PATHFINDER 2 (PF2; NCT05155605) assesses its safety and performance in a large, diverse intended-use population.

Methods

PF2 is a prospective, multicenter, interventional study that enrolled participants (ppts) aged ≥50y with no clinical suspicion of cancer and no cancer diagnosis/treatment in the past 3y. Primary objectives were safety and performance of the MCED test. Ppts with an MCED cancer signal detected (positive) result underwent dx evaluation based on predicted CSO(s). This prespecified initial analysis included ppts with 12m follow-up (fu) as of Dec 31, 2024. A 3y fu is planned.

Results

35,878 ppts were enrolled. Of 23,161 performance analyzable ppts with 12m fu, 216 (0.93%) had a positive MCED test. Specificity was 99.6% (95% CI 99.5-99.7%); positive predictive value (PPV) was 61.6% (54.9-67.8%). First CSO prediction accuracy was 91.7% (85.8-95.3%). Episode sensitivity during 12m fu was 73.7% (65.6-80.4%) in a prespecified subgroup of 12 cancers responsible for ⅔ of US cancer deaths and 40.4% (35.3-45.8%) in all cancers. Of 329 ppts with cancer, 200 had screen-detected cancers: 133 by MCED testing (114 new primaries; 19 recurrent), 20 by USPSTF A/B and 47 by USPSTF C recommended screening tests. Of 133 MCED-detected cancers (MCED cancer detection rate: 0.57%), 75.2% do not have common screening options. Of 114 MCED-detected new primaries, 53.5% were stage I-II; 69.3% were stage I-III. Median time to dx resolution was 46d (IQR 42-59). Of 25,114 safety analyzable ppts, 159 (0.6%) had a protocol-directed invasive procedure. Invasive procedures were ∼2x more common for ppts dx with cancer vs not dx after a positive MCED test.

Conclusions

MCED testing increased the number of screen-detected cancers nearly 7-fold when added to USPSTF A/B recommended screening (3-fold when added to USPSTF A/B/C). Most MCED-detected new primaries were early stage. With PPV exceeding that of standard of care screening tests and a favorable safety profile, these initial PF2 results support the MCED test’s use for population-scale screening.

Clinical trial identification

NCT05155605.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Jennifer Hepker, PhD, and Alexandra L. Thomas, PhD, of Citrus Health Group (Chicago, IL, USA), and was funded by GRAIL, Inc.

Xiuning Le MD PhD; ESMO 2025: Sevabertinib Success for Patients with HER2-Mutated Non-Small Cell Lung Cancer in SOHO-01 Study

Audio Medica News — Fri, 31 Oct 2025 12:29:54 +0000

An interview with: Xiuning Le MD PhD, Medical Oncologist, Department of Thoracic Medicine, UT MD Anderson Cancer Center, Houston TX

BERLIN, Germany—Mutations in the HER2 molecule can be found in a few per cent of non-small cell lung cancers, and these can now be targeted by the new drug sevabertinib that can bring benefit to patients who have the mutation. That’s according to findings from the SOHO-01 study reported at the 2025 Annual Congress of the European Society of Clinical Oncology.

After her talk at the congress, first author Xiuning Le MD PhD, who is a medical oncologist in the Department of Thoracic Medicine, at the University of Texas MD Anderson Cancer Center, in Houston, talked about the new data with Audio Journal of Oncology reporter Peter Goodwin:

Audio Journal of Oncology; Xiuning Le MD PhD

IN: “[GOODWIN] I am at the European Society for Medical ….OUT: ……. For the Audio Journal of Oncology, I’m Peter Goodwin” 10: 18secs

2025 ESMO Berlin ABSTRACT LBA75:

Sevabertinib (BAY 2927088) in advanced HER2-mutant non-small cell lung cancer (NSCLC): Results from the SOHO-01 study

Speaker: Xiuning Le (Houston, United States of America)

Authors: Xiuning Le (Houston, United States of America) Tae Min Kim (Seoul, Republic of Korea) Xiaorong Dong (Wuhan, China) Herbert Ho Fung Loong (Hong Kong, Hong Kong SAR, China) Nicolas Girard (Paris, France) Shun Lu (Shanghai, China) Hye Ryun Kim (Seoul, Republic of Korea) Boon-Cher Goh (Singapore, Singapore) Arsela Prelaj (Milan, Italy) Yong Fang (Hangzhou, China) Lin Wu (Changsha, China) Yuki Shinno (Tokyo, Japan) Gennaro Daniele (Rome, Italy) Tsung-Ying Yang (Taichung City, Taiwan) Gerrina Ruiter (Amsterdam, Netherlands) Jun Zhao (Beijing, China) Jan Christoph Brase (Basel, Switzerland) Rui Li (Whippany, United States of America) Paolo Grassi (Milan, Italy) Lin Li (Beijing, China)

Background

Sevabertinib is a potent, reversible, oral HER2 tyrosine kinase inhibitor with FDA Breakthrough Therapy Designation and Priority Review for pretreated patients (pts) with advanced HER2-mutant NSCLC. We report updated efficacy and safety in pretreated and treatment-naïve pts with HER2-mutant NSCLC in the open-label, multicenter Phase I/II SOHO-01 study.

Methods

Pts with HER2-mutant NSCLC were treated with sevabertinib 20 mg twice daily in 3 cohorts: Cohort D, previous systemic therapy but naïve to HER2 ex20ins-targeted therapy; Cohort E, previous HER2-targeted antibody-drug conjugates; Cohort F, naïve to systemic anti-cancer therapy for advanced disease. The primary endpoint was objective response rate (ORR) by RECIST v1.1 and blinded independent central review. Secondary endpoints were duration of response (DoR) and progression-free survival (PFS).

Results

At the data cut-off (June 27, 2025), 209 pts with HER2-mutant NSCLC were treated: 81 (D), 55 (E), and 73 (F). ORR (95% CI) was 64% (53, 75; D), 38% (25, 52; E), and 71% (59, 81; F). Median (95% CI) DoR was 9.2 (6.3, 13.5; D), 8.5 (5.6, 16.4; E), and 11.0 (8.1, not evaluable; F) months; 12-month DoR rates (95% CI) were 42% (27, 57; D) and 29% (5, 53; E). Median PFS (95% CI) was 8.3 (6.9, 12.3; D) and 5.5 (4.3, 8.3; E) months, and not reached (F). In Cohort D, pts with baseline brain metastases had a similar ORR to those without (61% vs 65%). Among pts with HER2 tyrosine kinase domain (TKD) mutations, those with Y772_A775dupYVMA had a higher ORR (78% vs 57%) and median PFS (12.2 vs 7.0 months) than those with other HER2 TKD mutations. Overall, grade ≥3 treatment-related adverse events (TRAEs) were reported in 31% of pts. Diarrhea was the most commonly reported TRAE, mostly grade 1/2 (grade 3: 14%). TRAEs led to treatment discontinuation in 3% of pts; none due to diarrhea. There were no reports of interstitial lung disease or pneumonitis.

Conclusions

Sevabertinib showed rapid and durable responses with a manageable safety profile in pretreated and treatment-naïve pts with advanced HER2-mutant NSCLC. These data support sevabertinib as a potential practice-changing, new targeted therapy for pts with HER2-mutant NSCLC.

Clinical trial identification: NCT05099172, March 28, 2025.

Editorial acknowledgement: Alice Xue, MSc, Erica Sedgwick, MSc, and Rachel Fairbanks, BA, of Caudex, IPG Health Medical Communications, provided medical writing and editorial assistance in the development of this abstract, funded by Bayer AG.

Legal entity responsible for the study: Bayer AG.

New England Journal of Medicine

https://www.nejm.org/doi/full/10.1056/NEJMoa2511065

ESMO 2025; Christof Vulsteke MD PhD: Perioperative Enfortumab Vedotin Therapy With Pembrolizumab Boosts Event-Free and Overall Survival in Platinum-Ineligible Patients with Muscle-Invasive Bladder Cancer: KEYNOTE-905 study

Audio Medica News — Thu, 30 Oct 2025 13:12:29 +0000

An interview with: Christof Vulsteke MD PhD, Medical Oncologist, Head of the Integrated Cancer Center Ghent, Belgium

BERLIN, Germany—Patients with muscle invasive bladder who were ineligible for cisplatin chemotherapy gained large, clinically meaningful and statistically significant benefits from treatment with the antibody drug conjugate enfortumab vedotin combined with pembrolizumab checkpoint inhibition in the phase three KEYNOTE-905 study.

At the 2025 Annual Congress of the European Society for Medical Oncology (ESMO) Medical Oncologist Christof Vulsteke, Head of the Integrated Cancer Centre in Ghent, Belgium, reported marked improvements of event-free and overall survival among patients treated with the new combination, in comparison with those receiving standard radical cystectomy plus pelvic lymph node dissection. After his talk in Berlin he gave more details to Audio Journal of Oncology reporter Peter Goodwin:

Audio Journal of Oncology: Christof Vulsteke MD PhD; IN: “[GOODWIN] I am at the ESMO meeting in Berlin ……OUT: …Goodwin for the Audio Journal of Oncology, Goodbye 7:12 secs

ESMO 2025 ABSTRACT No. LBA2

“Perioperative (periop) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: The phase III KEYNOTE-905 study”

Speaker: Christof Vulsteke (Gent, Belgium)

Authors:

Christof Vulsteke (Gent, Belgium) Hristos Kaimakliotis (Indianapolis, United States of America) Pongwut Danchaivijitr (Bangkok, Thailand) Maksym Y. Sabadash (Lviv, Ukraine) Alejo Rodriguez-Vida (Barcelona, Spain) Zhentao Zhang (Fort Wayne, United States of America) Vagiz Atduev (Nizhny Novgorod, Russian Federation) Yunus Emre Goger (Konya, Türkiye) Steffen Rausch (Tuebingen, Germany) Seok Ho Kang (Seoul, Republic of Korea) Yohann Loriot (Villejuif, France) Jens Bedke (Stuttgart, Germany) Matthew D. Galsky (New York, United States of America) Peter H. O’Donnell (Chicago, United States of America) Michael Mihm (Chicago, United States of America) Changting Meng (Groton, United States of America) David Huang (Rahway, United States of America) Chethan Ramamurthy (North Wales, United States of America) Blanca Homet Moreno (Madrid, Spain) Anders Ullén (Stockholm, Sweden)

Background

Radical cystectomy + pelvic lymph node dissection (RC + PLND) is the standard treatment for pts with MIBC who are cisplatin-ineligible. Periop therapy may improve outcomes in these pts.

Methods

The phase 3 KEYNOTE-905/EV-303 study (NCT03924895) evaluated efficacy and safety of periop EV + pembro and RC + PLND vs RC + PLND in adult pts with MIBC (T2-T4aN0M0 or T1-T4aN1M0) who were cisplatin-ineligible or declined cisplatin. Pts were randomized 1:1 to EV + pembro (3 cycles EV 1.25 mg/kg on d1 and d8 + pembro 200 mg on d1 Q3W, followed by RC + PLND, then 6 cycles EV + 14 cycles pembro) vs control (RC + PLND only). Study therapy continued until progression, unacceptable adverse events (AEs), withdrawal of consent, or completion of planned treatment. The primary endpoint was event-free survival (EFS) by blinded independent central review. Secondary endpoints were overall survival (OS; key), pathological complete response (pCR) rate (key), and safety.

Results

170 pts were randomized to EV + pembro and 174 pts to control. >80% of pts were cisplatin-ineligible per Galsky criteria. As of Jun 6, 2025, median follow-up time was 25.6 mo (range, 11.8–53.7). 149 pts (87.6%) in the EV + pembro arm and 156 (89.7%) in the control underwent surgery. EV + pembro significantly improved EFS (median not reached [NR] vs 15.7 mo; HR 0.40; 95% CI 0.28–0.57; P<.001), OS (NR vs 41.7 mo; HR 0.50; 95% CI 0.33–0.74; P<.001), and pCR rate (57.1% vs 8.6%; estimated difference 48.3%; 95% CI 39.5–56.5; P<.001) vs control. Treatment-emergent AEs occurred in 100% (gr ≥3, 71.3%) of pts in the EV + pembro arm and 64.8% (gr ≥3, 45.9%) in the control. Most frequent gr ≥3 AE of special interest (based on distinct prespecified lists for each drug) was severe skin reactions (grouped term; 11.4%) for pembro, and skin reactions (grouped term; 10.8%) for EV.

Conclusions

Adding periop EV + pembro to surgery significantly and meaningfully improved EFS, OS, and pCR rate in pts with MIBC who were predominantly cisplatin-ineligible. The safety profile of EV + pembro was manageable and consistent with prior reports. This is the first perioperakthrough regimen to improve outcomes vs RC + PLND in this setting and may be a new standard of care.

Clinical trial identification: NCT03924895.

Xichun Hu MD PhD; ESMO 2025: Antibody Drug Conjugate Trastuzumab Botidotin Outperforms Trastuzumab Emtansine in Patients with HER2-Positive Unresectable or Metastatic Breast Cancer

Audio Medica News — Tue, 28 Oct 2025 22:00:27 +0000

An interview with: Xichun Hu MD PhD, Professor, Director, Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China

BERLIN, Germany—In a head-to-head comparison of two antibody drug conjugates used to treat unresectable or metastatic breast cancer, patients treated with trastuzumab botidotin lived more than twice as long before disease progression than those in the control arm receiving trastuzumab emtansine (T-DM1). This finding was announced by Chinese researchers at the 2025 Annual Congress of the European Society of Medical Oncology.

Lead author Xichun Hu MD PhD, Professor, Director, Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China talked about the findings of his groups phase three randomized controlled study with Audio Journal of Oncology reporter Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Xichun Hu MD PhD

IN: “[GOODWIN] Peter Goodwin at ESMO ..OUT: ..of Oncology, I’m Peter Goodwin 8:30 sec

ESMO ABSTRACT LBA24

“Trastuzumab botidotin vs trastuzumab emtansine (T-DM1) in HER2-positive unresectable or metastatic breast cancer: Results from a randomized phase III study”

Speaker: Xichun Hu (Shanghai, China)

Authors:

Xichun Hu (Shanghai, China) Jian Zhang (Shanghai, China) Quchang Ouyang (Changsha, China) Qingyuan Zhang (Harbin, China) Huihui Li (Jinan, China) Xu Wang (Tianjin, China) Ying Wang (Guangzhou, China) Yongmei Yin (Nanjing, China) Shusen Wang (Guangzhou, China) Yuanting Gu (Zhengzhou, Algeria) Tao Sun (Shenyang, China) Jingfen Wang (Linyi, China) Xinhong Wu (Wuhan, China) Fanfan Li (Hefei, China) Xi Chen (Fuzhou, China) Man Li (Dalian, China) Jin Yang (Xi’an, Shaanxi Province, China) Hua Yang (Baoding, China) Xiaoping Jin (Chengdu, China) Junyou Ge (CHENGDU, China)

Lecture Time

ASTRACT

Background

Trastuzumab botidotin (A166) is a HER2-directed ADC developed using a stable, protease-cleavable valine-citrulline linker conjugated to the anti-microtubule agent Duo-5. In a phase 1 study, A166 showed promising activity in heavily pretreated patients (pts) with HER2+ breast cancer (BC). Here, we first report the results from a phase 3 study (NCT06968585).

Methods

Pts with HER2+ unresectable or metastatic BC who had received at least one prior anti-HER2 therapy were randomized (1:1) to receive A166 (4.8 mg/kg Q3W) or T-DM1 (3.6 mg/kg Q3W) until disease progression or unacceptable toxicity. The primary endpoint was PFS by BICR per RECIST v1.1.

Results

A total of 365 pts were randomized (median age 55 years; 73.4% with visceral metastases; 53.4% received ≥2 prior anti-HER2 therapies; 55.9% had prior pyrotinib). As of 26 April 2025, median follow-up was 14.9 mo. Median PFS was significantly longer in A166 than in T-DM1 (11.1 mo vs 4.4 mo; HR 0.39 [95% CI 0.30-0.51], p<0.0001). PFS benefit with A166 was consistently observed regardless of prior lines of anti-HER2 therapy (HR 0.36 for 1 prior line; HR 0.39 for ≥2 prior lines). ORR by BICR was 76.9% vs 53.0%, and mDOR was 12.2 mo vs 5.7 mo. Although OS data were immature, a trend toward benefit was observed in A166 (HR 0.62; 95% CI, 0.38-1.03). Grade ≥3 TEAEs occurred in 69.8% of pts in A166 and 63.7% in T-DM1. The most common grade ≥3 TEAEs (≥5%) were corneal disorder, dry eye, and vision blurred in A166, and platelet count decreased, neutrophil count decreased, hypokalemia, and GGT increased in T-DM1. Among A166-treated pts who experienced any-grade ocular AEs, instrumental activities of daily living (ADL) limitations occurred in 37 (20.3%) pts, and self-care ADL limitations in 13 (7.1%) pts; these resolved in 32 (86.5%) and 12 (92.3%) pts, respectively. TEAEs led to discontinuation in 1.1% of pts in A166 and 3.8% in T-DM1. No TEAE led to death in A166, compared with 1.1% in T-DM1.

Conclusions

A166 demonstrated statistically significant and clinically meaningful improvement in PFS compared with T-DM1, with a manageable safety profile in pts with HER2+ unresectable or metastatic BC. These results position A166 as a potential new therapeutic option for HER2+ disease.

Clinical trial identification

NCT06968585.

Legal entity responsible for the study

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Funding

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Disclosure

Jin, J. Ge: Financial Interests, Institutional, Full or part-time Employment: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.

Xichun Hu MD, PhD

Medical Oncology

Xuhui, Shanghai, China

Xi-Chun Hu, M.D., Ph. D., is currently a Professor, Director of the Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China. Dr. Hu has published more than 170 papers in the journals, such as Lancet Oncology, JCO, and International Journal Cancer, and 5 book chapters. He is vice editor of the ABC (Advanced breast cancer) guideline (Chinese version) and one of the leading authors of the CBCS (Chinese Breast Cancer Society) guideline for breast cancer diagnosis and treatment which is updated biannually.

Dr. Hu is an active member of the American Society of Clinical Oncology, General secretary & Member of the standing committee of CBCS (Chinese Breast Cancer Society), Vice-chair of Shanghai Breast Cancer Society, Member of the Standing Academic Committee of CSCO (Chinese Society of Clinical Oncology).

Dr. Hu’s major interest is in the diagnosis and management of breast cancer, both in the clinic and in the laboratory, and in phase I trial on new anticancer agents. His laboratory interests and contributions have been in the area of serum tumor markers, epigenetic alteration and gene expression, and detection of residual disease. He and his laboratory are now concentrating on translational research on triple-negative breast cancer and angiogenesis.

Martin Wermke MD; ESMO 2025: Initial Therapy with Bi-Specific T-cell Engager Tarlatamab Promises Better Outcomes in Patients with Small Cell Lung Cancer

Audio Medica News — Mon, 27 Oct 2025 14:42:37 +0000

An interview with: Martin Wermke MD, TU Dresden, NCT/UCC Early Clinical Trial Unit and Medical Clinic, Poliklinik I, Natural Centre for Tumor Diseases, Dresden, Germany

BERLIN, Germany—The prospect of markedly better outcomes for patients with small cell lung cancer, with “encouraging initial survival outcomes”, was raised by findings from the DeLLphi-303 study, reported at the European Society for Medical Oncology (ESMO) 2025 Annual Congress. The bi-specific T-cell engager drug tarlatamab was included with initial therapy for patients with extensive stage small cell lung cancer.

Martin Wermke MD, from TU Dresden, Director of the NCT/UCC Early Clinical Trial Unit and of the Medical Clinic, Poliklinik I, Natural Centre for Tumor Diseases in Dresden, Germany reported the latest study data to the ESMO congress. After his talk he gave the details to our reporter Peter Goodwin:

Audio Journal of Oncology; Martin Wermke MD: ”[GOODWIN] Peter Goodwin here at the ESMO meeting ………….of Oncology, I’m Peter Goodwin.” 6:16secs

https://pubmed.ncbi.nlm.nih.gov/40934933/

ESMO ABSTRACT 2757O

Tarlatamab with first-line chemoimmunotherapy for extensive stage small cell lung cancer (ES-SCLC): DeLLphi-303 study

Speaker: Martin Wermke (Dresden, Germany)

Authors

Martin Wermke (Dresden, Germany) Sally Lau (Toronto, Canada) Mor T. Moskovitz (Petah Tikva, Israel) Ingel Demedts (Roeselare, Belgium) Kelly Paulson (Seattle, United States of America) Aurélie Swalduz (Lyon, France) Cornelius Waller (Freiburg, Germany) Luis Paz-Ares (Madrid, Spain) Makoto Nishio (Koto-ku, Japan) Michael Boyer (Camperdown, Australia, NSW) James Chih-Hsin Yang (Taipei City, Taiwan) Amanda Parkes (Thousand Oaks, United States of America) Yuyang Zhang (Thousand Oaks, United States of America) Ali Hamidi (Thousand Oaks, United States of America) Mukul Minocha (Thousand Oaks, United States of America) Pedro F. Simoes da Rocha (Barcelona, Spain)

Background: Tarlatamab with anti-PD-L1 achieved notable survival outcomes with manageable safety as maintenance therapy following 1L platinum-etoposide chemotherapy and anti-PD-L1 (1L chemo-IO) for ES-SCLC. In this phase Ib study (parts 2, 4, 7), the safety and efficacy of adding tarlatamab to 1L chemo-IO was assessed.

Methods: Patients (pts) had received 1 cycle of 1L chemo-IO prior to enrollment. On study, pts received 3 cycles of tarlatamab + 1L chemo-IO followed by tarlatamab + anti-PD-L1 Q3W until progression. Tarlatamab was administered 20 mg Q3W with a 1 mg step dose. Primary endpoints included dose-limiting toxicities (DLTs), treatment-emergent (TE), and treatment-related (TR) adverse events (AEs). Key secondary endpoints were objective response (OR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Results: Of 96 pts enrolled, 3 (3%) had DLTs. TEAEs and TRAEs were reported in all pts. The most common TRAEs were cytokine release syndrome (CRS, 56%), anemia (54%), and dysgeusia (46%). Grade (Gr) ≥ 3 TRAEs occurred in 72 pts (75%), most commonly neutropenia/neutrophil count decreased (44%), anemia (23%), and lymphopenia/lymphocyte count decreased (11%), primarily within the first two cycles. CRS (54% Gr 1-2; 2% Gr 3-4) and ICANS and associated neurological events (5% Gr 1-2; 1% Gr 3) TRAEs were mostly low grade. Other immune-related AEs were rare (2%). From a baseline scan after 1 cycle of 1L chemo-IO, OR rate following tarlatamab addition to 1L chemo-IO was 71%, with median DOR of 11.0 months (mo) (95% CI 6.7-not estimable). Median PFS was 9.0 mo. With a median follow-up time of 11.3 mo, the Kaplan-Meier estimate of OS at 12 mo was 81% (Table). Results from further follow-up will be presented. Table: 2757O

Safety and efficacy of tarlatamab + chemoimmunotherapy as 1L treatment for ES-SCLC

Conclusions: The combination of tarlatamab with chemo-IO for 1L treatment of ES-SCLC demonstrated manageable safety with encouraging initial survival outcomes, supporting further investigation of this combination in the phase III DeLLphi-312 study.

Clinical trial identification: NCT05361395.

Editorial acknowledgement

Medical writing support for the development of this abstract was provided by Sukanya Raghuraman, PhD, of Cactus Life Sciences, part of Cactus Communications, and Liz Leight, PhD, an employee of Amgen Inc., and was funded by Amgen Inc.

Legal entity responsible for the study: Amgen Inc.

Funding: Amgen Inc.

John P. Crown MD MBA: ESMO 2025, Berlin: Adjuvant Ribociclib Brought Longer Freedom from Metastases for Patients with HR+/HER2- Early Breast Cancer: NATALEE Five Year Outcomes

Audio Medica News — Fri, 24 Oct 2025 10:15:07 +0000

An interview with: John P. Crown MD MBA, Consultant Medical Oncologist, St. Vincent’s University Hospital, Dublin, Professor of Translational Cancer Research, Dublin City University, Professor of Medicine, University College Dublin Ireland.

BERLIN, Germany—Patients with high-risk node-negative ER-positive HER2-negative early breast cancer who had the CDK 4/6 inhibitor drug ribociclib added to their non-steroidal aromatase inhibitor (AI) adjuvant therapy after surgery had significantly longer freedom from progression to invasive disease compared with patients receiving the AI alone. This is according to five-year data from the NATALEE trial reported at the 2025 Annual Congress of the European Society for Medical Oncology.

Professor John P. Crown MD MBA, Consultant Medical Oncologist, from St. Vincent’s University Hospital in Dublin gave reporter Peter Goodwin the latest details:

Audio Journal of Oncology, John P. Crown MD MBA,

IN: “[GOODWIN] I am at the ESMO meeting, 2025, in Berlin ….OUT: signing off for the Audio Journal of Oncology.” 11:24 secs

2025 ESMO: Proffered Paper Friday 14:00 Oct 17, 2025

Abstract Title:

LBA14 – Adjuvant ribociclib (RIB) plus nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2− early breast cancer (EBC): NATALEE 5-year outcomes

Speaker:

John P. Crown (Dublin, Ireland)

Authors:

John P. Crown (Dublin, Ireland) Daniil Stroyakovskiy (Moscow, Russian Federation) Denise Yardley (Chattanooga, United States of America) Chiun-Sheng Huang (Taipei City, Taiwan) Peter A. Fasching (Erlangen, Germany) Aditya Bardia (Los Angeles, United States of America) Stephen Chia (Vancouver, Canada) Seock-Ah Im (Seoul, Republic of Korea) Miguel Martin (Madrid, Spain) Binghe Xu (Beijing, China) Carlos H. Barrios (Porto Alegre, Brazil) Michael Untch (Berlin, Germany) Rebecca Moroose (Lake Mary, United States of America) Sara A. Hurvitz (Seattle, United States of America, CA) Gabriel N. Hortobagyi (Houston, United States of America) Dennis Slamon (Los Angeles, United States of America) Frances Visco (Washington, United States of America) Gonzalo Spera (Montevideo, Uruguay) Zheng Li (East Hanover, United States of America) Sherene Loi (Melbourne, Australia, VIC)

Background:

The phase 3 NATALEE trial demonstrated that adjuvant RIB + NSAI led to a statistically significant invasive disease–free survival (iDFS) benefit in pts with stage II and III HR+/HER2− EBC. We present a protocol-specified 5-year efficacy analysis.

Methods:

Pts with HR+/HER2− EBC were randomized 1:1 to RIB (400 mg/d; 3 weeks on/1 week off for 3 y) + NSAI (letrozole 2.5 mg/d or anastrozole 1 mg/d for 5 y) or NSAI alone. Men and premenopausal women received goserelin. Pts were included if they had anatomical stage IIA (if N1 [1-3 axillary lymph nodes] or N0 with additional high-risk factors), stage IIB, or stage III disease per AJCC, 8th ed. The primary end point of iDFS and secondary efficacy end points of distant disease–free survival (DDFS), distant relapse–free survival (DRFS), and overall survival (OS) were evaluated using Kaplan-Meier methods. Statistical comparisons were made by stratified log-rank test.

Results:

At data cutoff (May 28, 2025), all pts were off RIB treatment, and a similar proportion had completed 5 years of NSAI treatment in both arms (RIB + NSAI, 36.5%; NSAI alone, 34.4%). With a median iDFS follow-up of 55.4 months, RIB + NSAI demonstrated persistent iDFS benefit over NSAI alone (hazard ratio [HR], 0.716; 95% CI: 0.618-0.829; nominal 1-sided P<.0001). Absolute iDFS rates were 90.8% vs 88.0% at 3 y, 88.3% vs 83.9% at 4 y, and 85.5% vs 81.0% at 5 y (absolute improvement of 2.7%, 4.4%, and 4.5%, respectively). iDFS benefit was observed across subgroups, including N0 (HR, 0.606; 95% CI: 0.372-0.986). RIB + NSAI also demonstrated continued DDFS (HR, 0.709; 95% CI: 0.608-0.827) and DRFS (HR, 0.699; 95% CI: 0.594-0.824) benefit vs NSAI alone. A positive trend for OS favoring RIB + NSAI (HR, 0.800; 95% CI: 0.637-1.003; nominal 1-sided P=.026) continues to emerge. No new safety signals were observed with a median follow-up time of approximately 2 years after RIB completion.

Conclusions:

In this 5-year landmark analysis with mature efficacy data, RIB + NSAI reduced the risk of invasive and distant disease recurrence compared with NSAI alone, including in pts with high-risk N0 disease. A positive trend for OS in favor of RIB + NSAI continues to emerge.

Javier C Cortés MD PhD: ESMO 2025, Berlin: Initial Therapy with Sacituzumab Govitecan Improves Progression-Free Survival in Patients with Newly-Diagnosed Metastatic Triple Negative Breast Cancer—ASCENT-03 study

Audio Medica News — Thu, 23 Oct 2025 12:22:50 +0000

An interview with: Javier C Cortés MD PhD, Breast Cancer Medical Oncologist, IOB Madrid, Institute of Oncology, Madrid, and International Breast Cancer Centre, Barcelona, Spain

BERLIN, Germany—Treatment with the antibody drug conjugate (ADC) sacituzumab govitecan (that targets the Trop-2 cancer-associated protein, delivering a cytotoxic topoisomerase inhibitor payload) has significantly improved progression-free survival in patients with newly-diagnosed metastatic triple-negative breast cancer who were not candidates for treatment with immune checkpoint inhibition and had received no prior therapy.

At the European Society for Medical Oncology (ESMO) 2025 Annual Congress Javier C Cortés MD PhD from the Institute of Oncology in Madrid and the International Breast Cancer Centre in Barcelona reported data from the ASCENT-03 study showing that treatment with sacituzumab govitecan brought clinically meaningful benefits with toxicities that were found to be manageable.

At the congress Cortés talked about the new findings with Peter Goodwin:

Audio Journal of Oncology: Javier C Cortes MD PhD

“[GOODWIN] Peter Goodwin here in Berlin …..……….Audio Journal of Oncology, I’m Peter Goodwin. 9:47secs

ESMO ABSTRACT:

LBA20 – “Primary results from ASCENT-03: A randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i)”

Speaker: Javier C. Cortés (Barcelona, Spain)

Authors: Javier C. Cortés (Barcelona, Spain), Aditya Bardia (Los Angeles, United States of America), Kevin Punie (Antwerp, Belgium), Carlos H. Barrios (Porto Alegre, Brazil), Sara A. Hurvitz (Seattle, United States of America, CA),Andreas Schneeweiss (Heidelberg, Germany), Joohyuk Sohn (Seoul, Republic of Korea), Eriko Tokunaga (Fukuoka, Japan), Adam M. Brufsky (Pittsburgh, United States of America, PA), Yeon Hee Park (Seoul, Republic of Korea), Binghe Xu (Beijing, China), Roberto Hegg (São Paulo, Brazil), Mafalda Oliveira (Barcelona, Spain), Alessandra Fabi (Rome, Italy), Natalya Vaksman (Miami, United States of America), Theresa Valdez (Miami, United States of America), Xinrui Zhang (Miami, United States of America), Catherine Lai (Foster City, United States of America, CA), Sara M. Tolaney (Boston, United States of America, MA)

Background

Significant PFS benefit was observed with SG vs chemo in pretreated metastatic (m)TNBC (ASCENT) and with SG + pembrolizumab vs chemo + pembrolizumab in first-line (1L) PD-L1+ mTNBC (ASCENT-04). For pts with mTNBC who cannot receive PD-(L)1i, treatment options are limited. We report primary results from the randomized phase 3 ASCENT-03 study (NCT05382299) of 1L SG vs chemo in pts with locally advanced unresectable or mTNBC who are unable to receive a PD-(L)1i.

Methods

Pts had centrally confirmed PD-L1− mTNBC (defined as combined positive score [CPS] < 10) or PD-L1+ mTNBC (CPS ≥ 10) but were unable to receive PD-(L)1i due to a comorbidity or prior use in the curative setting. Randomization (1:1) to SG (10 mg/kg IV, days 1 & 8 in 21-day cycles) or chemo (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin) was stratified by disease status and geography. The primary end point was PFS by BICR. Key secondary end points included overall survival (OS), ORR and DOR by BICR, and safety.

Results

558 pts (279 in each group) with mTNBC were randomized. With a median follow-up of 13.2 mo, SG showed a significant improvement in median PFS vs chemo (9.7 vs 6.9 mo; HR, 0.62; 95% CI, 0.50-0.78; P < .0001); median DOR was 12.2 mo vs 7.2 mo (Table). OS data were immature. The most frequent grade ≥ 3 TEAEs were neutropenia (43%) and diarrhea (9%) with SG and neutropenia (41%) and anemia (16%) with chemo.

Conclusions

SG led to a statistically significant and clinically meaningful improvement in PFS and more durable responses vs chemo in 1L mTNBC. The safety profile of SG was manageable and consistent with its known profile; treatment discontinuation rate due to TEAEs was lower with SG vs chemo. These data support SG as a potential new standard of care for pts with previously untreated mTNBC who are unable to receive a PD-(L)1i. Table: LBA20

Clinical trial identification

NCT05382299.

Editorial acknowledgement

Editorial assistance was provided by Peggy Robinet, PharmD, PhD, and Sonal S. Joshi, PhD, of Parexel, and funded by Gilead Sciences, Inc.

Legal entity responsible for the study

Gilead Sciences, Inc.

Funding

Gilead Sciences, Inc.

PRESS RELEASE:

ASCENT-03: Trodelvy® Demonstrates Highly Statistically Significant & Clinically Meaningful Improvement in Progression Free Survival in Patients With First-line Metastatic Triple-Negative Breast Cancer Who Are Not Candidates for Checkpoint Inhibitors

– Second Positive Phase 3 Trial in First-line Metastatic TNBC Where Trodelvy Has Demonstrated a Clinically Meaningful Benefit Versus Standard of Care Chemotherapy –

– Trodelvy Has the Potential to Be the Backbone of Treatment and the First Antibody-Drug Conjugate for All Patients Across First-line Metastatic TNBC –

FOSTER CITY, Calif.–(BUSINESS WIRE)– Gilead Sciences, Inc. (Nasdaq: GILD) today announced positive topline results from the Phase 3 ASCENT-03 study of Trodelvy® (sacituzumab govitecan-hziy). The study met its primary endpoint, demonstrating a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to chemotherapy in patients with first-line metastatic triple-negative breast cancer (mTNBC) who are not candidates for PD-1/PD-L1 inhibitors, meaning they are PD-L1 negative or are ineligible to receive immunotherapy.

“Almost half of the patients diagnosed with metastatic triple-negative breast cancer do not receive treatment beyond first-line, demonstrating an urgent need for innovative treatment options in this early setting,” said Dr. Javier Cortes, Head of the International Breast Cancer Center in Spain and principal investigator of the ASCENT-03 study. “Traditional chemotherapy has been the standard of care for early treatment of metastatic triple-negative breast cancer, and we know that therapeutic advances in this disease area serve a critical unmet need for patients and the broader oncology community.”

Together with the recently announced positive results from the ASCENT-04 study evaluating Trodelvy plus Keytruda® in patients with previously untreated PD-L1+ metastatic TNBC, Trodelvy now has the potential to be the backbone treatment for all patients across first-line mTNBC. Detailed data from the ASCENT-04 study will be shared during the American Society of Clinical Oncology (ASCO) meeting taking place May 30 – June 3, 2025.

“The ASCENT-03 outcome represents the first clinically meaningful advance for this patient population in over 20 years versus chemotherapy,” said Dietmar Berger, MD, PhD, Chief Medical Officer, Gilead Sciences. “By addressing this aggressive and difficult to treat disease earlier, we can potentially improve treatment options for the high unmet need that patients with metastatic triple-negative breast cancer face.”

The safety profile of Trodelvy in the ASCENT-03 study was consistent with prior studies, and no new safety signals were identified in this patient population. Overall survival (OS) is a key secondary endpoint and was not mature at the time of PFS primary analysis. No OS detriment was observed. Gilead will continue to monitor OS outcomes, with ongoing patient follow-up and further analysis planned.

Detailed results from the ASCENT-03 study will be presented at a future medical meeting and discussed with regulatory authorities. The use of Trodelvy in first-line mTNBC is investigational, and the safety and efficacy of this use have not been established.

Healthcare professionals have well-established experience with Trodelvy, which has shown generally consistent outcomes across both clinical trials and real-world studies in 60,000+ patients across 50+ countries over approximately five years. It is the only antibody-drug conjugate (ADC) with four positive Phase 3 trials in HER2- (IHC 0, IHC 1+ or IHC 2+/ISH–) metastatic breast cancer (mBC), and remains the only approved Trop-2-directed ADC that has demonstrated meaningful survival advantages in two different types of metastatic breast cancers: 2L mTNBC and pre-treated HR+/HER2- mBC.

Trodelvy is a Category 1 preferred treatment for both currently approved indications per the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelinesi) and the only ADC with an ESMO Magnitude of Clinical Benefit Scale (MCBS) rating of 5 for mTNBC. Trodelvy also has an MCBS rating of 4 for women with HR+/HER2- mBC.

Currently, Gilead has additional ongoing Phase 3 studies investigating Trodelvy across HER2- (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer including the ASCENT-07 pivotal trial in patients with HR+/HER2- mBC who have received endocrine therapy, and the ASCENT-05 pivotal trial in patients with early-stage TNBC (eTNBC). Trodelvy is also being evaluated in additional Phase 3 studies across a range of tumor types, including in lung and gynecologic cancers.

Gilead would like to thank the patients, families, investigators and advocates who have contributed and continue to contribute to this important research. We remain committed to advancing care to address the unmet needs for the breast cancer community.

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About Triple-Negative Breast Cancer (In Patients Who Are Not Candidates for PD-1/PD-L1 inhibitors)

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer and has historically been difficult to treat, accounting for approximately 15% of all breast cancers. TNBC disproportionately impacts younger, pre-menopausal as well as Black and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited HER2. Due to the nature of TNBC, treatment options are extremely limited compared with other breast cancer types. TNBC has a higher chance of recurrence and metastases than other breast cancer types. The average time to metastatic recurrence for TNBC is approximately 2.6 years compared with 5 years for other breast cancers, and the relative five-year survival rate is much lower. Among women with metastatic TNBC, the five-year survival rate is 12%, compared with 28% for those with other types of mBC.

Chemotherapy remains the mainstay of treatment in first-line mTNBC patients who are not candidates for PD-1/PD-L1 inhibitors, and the need to improve outcomes continues to be high. In mTNBC overall, ~50% of patients do not receive treatment beyond 1L setting, demonstrating a need for additional effective earlier-line treatment options.

About the ASCENT-03 Study

The ASCENT-03 study is a global, open-label, randomized Phase 3 trial evaluating the efficacy and safety of sacituzumab govitecan compared with treatment of physician’s choice in patients with previously untreated, locally advanced, inoperable, or metastatic triple-negative breast cancer (mTNBC) whose tumors do not express PD-L1, or who are PD-L1 positive and previously treated with a PD-(L)1 inhibitor in the curative setting. ~540 patients were enrolled across multiple study sites worldwide.

Patients were randomized 1:1 to receive either sacituzumab govitecan (10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle) or treatment of physician’s choice, which included gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel. Treatment continued until blinded independent central review (BICR)-verified disease progression or unacceptable toxicity. Patients randomized to chemotherapy were eligible to crossover to sacituzumab govitecan upon disease progression.

The primary endpoint of the study is progression-free survival (PFS) as assessed by BICR according to RECIST v1.1. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), time to onset of response (TTR), patient-reported outcomes (PROs), and safety.

More information about ASCENT-03 is available at ClinicalTrials.gov: NCT05382299.

About Trodelvy

Trodelvy® (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect.

Trodelvy is currently approved in more than 50 countries for second-line or later metastatic triple-negative breast cancer (TNBC) patients and in more than 40 countries for certain patients with pre-treated HR+/HER2- metastatic breast cancer.

Trodelvy is currently being evaluated in multiple ongoing Phase 3 trials across a range of tumor types with high Trop-2 expression. These studies with Trodelvy, both in monotherapy and in combination with pembrolizumab, involve earlier lines of treatment for TNBC and HR+/HER2- breast cancer—including in curative settings—as well as in lung and gynecologic cancers, where previous proof-of-concept studies have demonstrated clinical activity.

INDICATIONS

TRODELVY® (sacituzumab govitecan-hziy) is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.

Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.

Trevor Leong MD: Operable Gastric or GE-Junction Adenocarcinoma: No Advantage from Neoadjuvant Radiotherapy

Audio Medica News — Mon, 13 Oct 2025 13:43:05 +0000

An interview with:

Trevor Leong MD, Peter McCallum Cancer Centre, Radiation Oncology Department, Melbourne, Australia

BARCELONA, Spain—Although pre-operative radiotherapy brought better response rates in patients resected for their gastric or GE-junction adenocarcinomas, there was no improvement in survival. This is the clear finding from a big, long-term study led by an Australian team.

The multi-continent, phase-three randomized TOP GEAR trial, headquartered in Sydney Australia, definitively found no benefit for overall or progression-free survival from adding radiation before surgery.

This clear finding was announced at the 2024 Annual Meeting of the European Society for Medical Oncology (ESMO), held in Barcelona, Spain

First author Trevor Leong MD, from the Radiation Oncology Department of the Peter McCallum Cancer Centre in Melbourne Australia, talked about the results with Peter Goodwin:

Trevor Leong MD interview (8mins 37 secs):

IN: “Resectable gastric or gastro-esophageal…. OUT: ,,’till next time, Good-bye.”

ESMO 2024, Barcelona, ABSTRACT:

03880-8/fulltext

“A randomised phase three trial of perioperative chemotherapy (CT) with or without pre-operative chemoradiotherapy (CRT) for resectable gastric cancer (AGITG TOPGEAR). Final results from an intergroup trial of AGITG, TROG, EORTC and CCTG”.

NEJM September 13, 2024:

https://www.nejm.org/doi/full/10.1056/NEJMoa2405195

TITLE:

“Preoperative Chemoradiotherapy for Resectable Gastric Cancer”

From: The Australasian Gastro-Intestinal Trials Group, National Health and Medical Research Council Clinical Trials Centre, Trans-Tasman Radiation Oncology Group, European Organisation for Research and Treatment of Cancer, and Canadian Cancer Trials Group.

JOURNAL Article: N Engl. J Med.:

“The addition of preoperative chemoradiotherapy to perioperative chemotherapy did not improve overall survival as compared with perioperative chemotherapy alone among patients with resectable gastric and gastroesophageal junction adenocarcinoma.”

Background

In Western countries, the current standard of care for resectable gastric cancer is periop CT. There is much interest in preop CRT, but comparison to periop CT alone is lacking. In TOPGEAR we hypothesized that adding preop CRT to periop CT would improve pathological complete response (pCR) rates and ultimately overall survival (OS) compared to periop CT alone.

Methods

This international phase 3 trial randomized patients with resectable adenocarcinoma of the stomach and gastro-esophageal junction to periop CT alone, or with preop CRT. The periop CT alone group received 3 cycles of epirubicin/cisplatin/5-fluorouracil (ECF) or 4 cycles of fluorouracil/leucovorin/oxaliplatin/docetaxel (FLOT) both pre- and post-operatively. The preop CRT group received one less cycle of preop chemotherapy followed by chemoradiotherapy (45 Gy in 25 fractions radiation plus infusional 5-FU ), and then the same postop chemotherapy. The primary endpoint was overall survival, and secondary endpoints included progression free survival (PFS), pCR rates, toxicity and quality of life.

Results

Between September 2009 and May 2021, 574 patients were enrolled from 70 sites across 15 countries in Australasia, Europe, and Canada; 288 to periop CT group and 286 to preop CRT group. Compared to periop CT alone, patients receiving preop CRT achieved a higher pCR rate (16.7% vs 8.0%), a higher rate of major pathological response (0 – <10% residual tumor: 49.5% vs 29.3%), and greater tumor downstaging following resection. After a median follow-up of 66.7 months, there was no significant difference in OS or PFS: median OS periop CT 49.4 months vs preop CRT 46.4 months; median PFS periop CT 31.8 months vs preop CRT 31.4 months. Preop CRT was not associated with increased perioperative treatment toxicity or a higher rate of surgical complications.

Conclusions

Despite improving pathological outcomes, the addition of preop CRT to periop CT does not improve overall survival compared to periop CT alone in patients with resectable gastric and gastro-esophageal junction adenocarcinoma.

Clinical trial identification

ACTRN12609000035224. Registered 30 May 2009; NCT01924819.

Legal entity responsible for the study

Australasian Gastro-Intestinal Trials Group (AGITG).

Funding

This work was supported by grants from the National Health and Medical Research Council: 1046425 and 2000711, Canadian Institutes of Health Research (CIHR) grant no. 119445, the Canadian Cancer Society Research Institute (CCSRI) grant no. 021039, the Health Research Council of New Zealand (HRC) International Investment Opportunities Fund: Contract no. 09/624, the EORTC Cancer Research Fund, and the Cancer Australia Priority-driven Collaborative Research Scheme: Project ID: 570996.

Disclosure

K.M. Haustermans: Financial Interests, Personal, Other, Clinical editor Radiotherapy & Oncology: Elsevier; Financial Interests, Institutional, Funding: IBA; Financial Interests, Institutional, Research Grant: Varian,

https://www.audiomedica.com/wp-content/2025/10/Trevor-Leong-ESMO-AJO-PRODUCTION-MASTER.mp3Editorial acknowledgement

Editorial and medical writing support was provided in accordance with Good Publication Practice guidelines by Lewis Cawkwell, PhD, of Parexel, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Domenica Lorusso MD PhD: Adding Early PD-1 Checkpoint Inhibition brings Big Reduction of Deaths for Patients with Newly Diagnosed Locally Advanced High-Risk Cervix Cancer

Audio Medica News — Mon, 06 Oct 2025 12:10:57 +0000

An interview with: Domenica Lorusso MD PhD, Director of the Gynaecological Oncology Unit, full Professor of Obstetrics and Gynaecology, Humanitas Hospital San Pio X, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy.

Both overall and progression-free survival were significantly improved when the anti-PD-1 agent pembrolizumab was added to standard chemoradiotherapy as initial treatment for patients with high-risk locally advanced cervical cancer.

Results from the randomized, double-blind, phase III KEYNOTE-A18 study of immunotherapy, used together with standard concurrent chemoradiotherapy among 1060 patients, were reported by a multinational team of researchers led from Italy to the 2024 Annual Congress of the European Society for Medical Oncology in Barcelona.

The study lead author Domenica Lorusso MD PhD, Director of the Gynaecological Oncology Unit at Humanitas Hospital San Pio X, in Milan, who is a Full Professor of Obstetrics and Gynaecology at Humanitas University, Rozzano, met up with Peter Goodwin to discuss the KEYNOTE-A18 findings.

Audio Journal of Onclogy: Domenica Lorusso MD PhD IN: “Immune checkpoint inhibition …..OUT: …….in Barcelona at the ESMO meeting”. Durn: 7:20 secs

ESMO Abstract 7090

Lorusso, Gynaecology Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS and Catholic University of the Sacred Heart, Rome, Italy

“Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: Overall survival results from the randomized, double-blind, phase III ENGOT-cx11/ GOG-3047/KEYNOTE-A18 study”

Background

At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study (NCT04221945), pembrolizumab (pembro) + concurrent chemoradiotherapy (CCRT) showed a statistically significant and clinically meaningful improvement in PFS vs placebo (pbo) + CCRT in patients (pts) with high-risk locally advanced cervical cancer (LACC). Based on this study, the US FDA has approved pembro + CCRT for pts with FIGO 2014 Stage III-IVA cervical cancer. We present the OS results from the second interim analysis.Methods

Eligible pts with newly diagnosed, previously untreated, high-risk LACC (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of lymph node status) were randomized 1:1 to 5 cycles of pembro 200 mg or pbo Q3W + CCRT, then 15 cycles of pembro 400 mg or pbo Q6W. CCRT included 5 cycles (optional 6th dose) of cisplatin 40 mg/m2 Q1W + EBRT then brachytherapy. Pts were stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), stage at screening (IB2-IIB vs III-IVA), and planned total radiotherapy dose (<70 Gy vs ≥70 Gy [EQ2D]). Primary endpoints are PFS per RECIST v1.1 by investigator and OS.Results

1060 pts were randomized to pembro + CCRT (n=529) or pbo + CCRT (n=531). At this analysis (January 8, 2024, data cutoff), median follow-up was 29.9 mo (range, 12.8-43.0). Pembro + CCRT showed a statistically significant improvement in OS compared with pbo + CCRT. The 36-mo OS rate was 82.6% with pembro + CCRT vs 74.8% with pbo + CCRT; median OS was NR in either group (HR=0.67 [95% CI, 0.50-0.90]; P=0.0040). The benefit of pembro + CCRT was generally consistent in all prespecified subgroups, including FIGO stages IB2-IIB (HR=0.89 [95% CI, 0.55-1.44]) and III-IVA (HR=0.57 [95% CI, 0.39-0.83]). Grade ≥3 TRAE incidence was 69.1% in the pembro + CCRT group and 61.3% in the pbo + CCRT group.

Conclusions

Pembro + CCRT showed a statistically significant and clinically meaningful improvement in OS vs pbo + CCRT in pts with high-risk LACC and had a manageable safety profile. These data provide further support for pembro + CCRT as a new standard of care for this population.

Clinical trial identification

NCT04221945; EudraCT: 2019-003152-37.

Editorial acknowledgement

Medical writing assistance was provided by Christine McCrary Sisk of Merck & Co., Inc., Rahway, NJ, USA. This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ,

Audio Journal of Oncology, October 6, 2025

James Larkin FRCP, PhD: CheckMate 067 Study 10-Year Data Show Advanced Melanoma Landscape Transformed by Combo Checkpoint Inhibitor Therapy

Audio Medica News — Fri, 03 Oct 2025 11:08:33 +0000

An interview with:

James Larkin FRCP, PhD, Medical Oncologist, Professor, Royal Marsden Hospital, London

Checkpoint inhibitor therapy for advanced melanoma has achieved sustained responses and long-term overall survival, transforming the prognosis for as many as half of all patients. 10-year survival outcomes from the phase Ill CheckMate 067 trial of nivolumab plus ipilimumab in advanced melanoma were reported at the 2024 Annual Meeting of the European Society for Medical Oncology (ESMO) held in Barcelona.

Peter Goodwin, talked with study author, James Larkin FRCP PhD, Professor and Medical Oncologist at the Royal Marsden Hospital in London.

Audio Journal of Oncology: James Larkin FRCP PhD: IN: “There’s been breath-taking progress ………OUT: join me then, Good-bye!” 14:57secs

SOURCE:

Annals of Oncology:

https://www.annalsofoncology.org/article/S0923-7534(24)03864-X/fulltext

ESMO Abstract LBA43

Larkin, Medicine Department, The Royal Marsden Hospital, London, UK

“10-y survival outcomes from the phase Ill CheckMate 067 trial of nivolumab plus ipilimumab in advanced melanoma”

Abstract LBA43

Larkin, Medicine Department, The Royal Marsden Hospital, London, UK

“10-y survival outcomes from the phase Ill CheckMate 067 trial of nivolumab plus ipilimumab in advanced melanoma”

Background

In CheckMate 067, improved survival with nivolumab plus ipilimumab (NIVO + IPI) or NIVO alone v IPI has been demonstrated in patients (pts) with advanced melanoma. We now provide the final CheckMate 067 results (minimum f/u 10 y), the longest reported in a phase 3 study of an anti–programmed death (PD)-1–based therapy for any tumor type.

Methods

Pts with untreated advanced melanoma (N = 945) were randomly assigned 1:1:1 and stratified by PD-ligand (L)1 status, BRAF mutation status, and metastasis stage to receive NIVO (1 mg/kg) + IPI (3 mg/kg) Q3W for 4 doses, followed by NIVO (3 mg/kg) Q2W; NIVO (3 mg/kg) Q2W + placebo; or IPI (3 mg/kg) Q3W for 4 doses + placebo until progression or unacceptable toxicity. Co-primary endpoints were OS and PFS with NIVO + IPI or NIVO v IPI; melanoma-specific survival (MSS) was an exploratory endpoint.

Results

After a 10-y minimum f/u, median OS was 71.9 mo with NIVO + IPI, 36.9 mo with NIVO, and 19.9 mo with IPI. OS HRs were 0.53 (95% CI, 0.44–0.65) with NIVO + IPI vIPI and 0.63 (0.52–0.76) for NIVO v IPI, and benefit was consistent across subgroups (including PD-L1 expression and BRAF mutation status). Median MSS was not reached (NR) with NIVO + IPI (> 120 mo), 49.4 mo with NIVO, and 21.9 mo with IPI. In pts who had PFS for ≥ 3 y, 10-y MSS rates were 96% with NIVO + IPI, 97% with NIVO, and 88% with IPI. Only 8 pts, 4 in the NIVO + IPI arm and 4 in the NIVO arm, progressed beyond 60-mo of f/u. For pts in the NIVO + IPI arm who discontinued treatment during induction due to a treatment-related adverse event, 10-y OS rates were the same as the ITT group (43%) and MSS rates were similar (50% v 52%). Table: LBA43”

James Larkin is a Medical Oncologist specialising in the treatment of cancers of the kidney and skin including melanoma.

Professor Larkin grew up in North Cornwall before taking a first in Natural Sciences from Cambridge University. He undertook clinical training in Oxford, qualifying in 1996. His general medical training was undertaken in London and in 2001 he won a Medical Research Council Research Fellowship for a Clinician, carrying out laboratory research leading to a PhD at the Institute of Cancer Research. His specialist training was completed at The Royal Marsden, where he was appointed as a Consultant in 2008.

His research is focussed on trying to understand cancer and its consequences better, as well as developing improved treatments, particularly with targeted therapies and immunotherapies. Globally, he is amongst the most highly cited researchers in both melanoma and kidney cancerThis link is external and opens in a new tab.

In 2018, he was elected as a Fellow of the Academy of Medical Sciences and in 2020 as an NIHR Senior Investigator. In 2022, he was appointed to roles as Head of The Royal Marsden Skin Unit, Royal Marsden Joint Training Programme Director for Medical Oncology and Lead of the Cancer Immunotherapy Theme at The Royal Marsden / Institute of Cancer Research NIHR Biomedical Research Centre.

Since 2024, he has hosted the educational podcast ‘Melanoma Matters’ with his US colleague Professor Sapna Patel, and in 2026 he will be Scientific Co-Chair of the Annual European Society of Medical Oncology meeting in Madrid.

Professor Larkin serves as a medical advisor to the patient advocacy group Melanoma UK, as a trustee of Action Kidney Cancer and sits on the Medical Advisory Board of the International Kidney Cancer Coalition.