Cyclin-Dependent Kinase Inhibition Overcomes Endocrine Resistance in Advanced Breast Cancer
DESCRIPTION
COPENHAGEN, Denmark—The efficacy of endocrine therapy in breast cancer was improved—in the MONALEESA-2 study—by the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib to letrozole therapy in post-menopausal patients with hormone-sensitive HER-2 negative advanced breast cancer. At the 2016 meeting of the European Society for Medical Oncology, ESMO, Gabriel Hortobagyi MD, Professor of Medicine at the University of Texas MD Anderson Cancer Center in Houston reported progression-free survival rates at 18 months increasing from 42 percent —with letrozole alone— to 65 percent with the first-line use of the combination of letrozole with ribociclib. Stephen R D Johnston MA FRCP PhD MD, Professor of Breast Cancer Medicine at the Royal Marsden Hospital and the Institute of Cancer Research in London described the findings as a “game-changer”.
INTERVIEW: Gabriel Hortobagyi MD, Professor of Medicine, University of Texas MD Anderson Cancer Center, Houston, USA
COMMENT: Stephen R D Johnston MA FRCP PhD MD Professor of Breast Cancer Medicine, Royal Marsden and Institute of Cancer Research, London, UK
TRANSCRIPT:
PETER: A randomized controlled phase III study of patients with advanced hormone-sensitive breast cancer has shown that resistance to endocrine therapy can be overcome by adding ribociclib, a drug inhibiting the cyclin-dependent kinase pathways on which some cancers depend.
INTERVIEW (Extract): Gabriel Hortobagyi MD
“Median progression-free survival for the control group—that is to say letrozole alone—is 14.7 months. Since fewer than 50 percent of the patients in the combination arm have developed progression there is not a firm median progression-free survival because the median has not been reached, but it’s expected to exceed 20 months or 24 months.”
PETER:
I’m Peter Goodwin reporting from Copenhagen at the 2016 meeting of the European Society for Medical Oncology, ESMO.
Gabriel Hortobagyi from Houston—who we just heard from—reported data from the MONALEESA-2 study looking at women with HER-2 negative hormone receptor positive tumors. The targeted agent ribociclib was added to letrozole endocrine therapy.
INTERVIEW: Gabriel Hortobagyi
“The big issue relates to the development of endocrine resistance. A little bit of background ………………………or in some cases dose reductions”
…..or perhaps several hundreds of thousands of women around the world.” 5:21secs
PETER: That was Gabriel Hortobagyi from the University of Texas MD Anderson Cancer Center in Houston.
And after he reported those findings, Stephen Johnston from London’s Royal Marsden Hospital added his appraisal. He compared the MONALEESA 2 findings with the positive and very similar— PALOMA-2 study findings— reported only a few months earlier—using another CDK inhibitor, palbociclib. He embraced the concept of using first-line targeted therapy in hormone sensitive breast cancer and the new findings from MONALEESA-2.
COMMENT: Stephen R D Johnston MA FRCP PhD MD, Professor of Breast Cancer Medicine, Royal Marsden Hospital and the Institute of Cancer Research, London.
“You’ve seen the data now. Very impressive separation of the curves improvement again from 14.7 to a median that has not even reached with a hazard ratio of 0.56. This is very significant improvement in benefit and efficacy but again I point you to the top of the curve. The separation is occurring early. And that tells us that the patients with either endocrine resistant disease and/or endocrine sensitive disease are benefiting. The efficacy and the toxicity data are very clear: It is clinically meaningful and significant improvement in efficacy endpoints, progression-free survival response rate and clinical benefit rate. That in effect was seen across all sub-groups and the toxicity is predictable and manageable. Is this a game changer? I think it probably is. Because we now have two randomized studies in a similar population within four months of each other that show a substantial improvement in progression-free survival. So I think that has to meet the criteria of level one evidence of being a game changer.” 1:12secs
(PALOMA-2
A Study of Palbociclib (PD-0332991) + Letrozole vs. Letrozole For 1st Line Treatment Of Postmenopausal Women With ER+/HER2- Advanced Breast Cancer (PALOMA-2))
PETER:
Stephen Johnston Professor of Breast Cancer Medicine at the Royal Marsden Hospital and the Institute of Cancer Research in London
For a final comment I asked Garbiel Hortobagyi how he thought the new insights from MONALEESA-2 should be applied:
INTERVIEW: Gabriel Hortobagyi
“We concluded after this analysis ………
…..or perhaps several hundreds of thousands of women around the world.” 1:53secs
Gabriel Hortobagyi from the MD Anderson Cancer Center in Houston, texas, talking to me at the 2016 ESMO congress in Copenhagen. For the Audio Journal of Oncology I’m Peter Goodwin.
