Erica L. Mayer, MD, MPH, Discusses New Targeted Therapies in Breast Cancer Treatment

Erica L. Mayer, MD, MPH, from Dana-Farber Cancer Institute, discussed the role of CDK4/6 inhibitors in treating metastatic hormone receptor positive breast cancer at the San Antonio Breast Cancer Symposium, held December 10-14, in San Antonio, Texas.

Transcription:
Over the past several decades, we’ve primarily been using endocrine monotherapy to treat metastatic hormone receptor positive breast cancer. However, over the past several years, we’ve had the introduction of new targeted therapies that we use in combination with an endocrine backbone, and the introduction of these agents have substantially improved progression-free and even overall survival for patients with metastatic hormone receptor positive, HER2-negative disease. We’ve had the introduction of the mTOR inhibitor everolimus, the CDK4/6 inhibitors palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (verzenio), and most recently in 2019 the PI3-Kinase inhibitor alpelisib. In my talk, I discussed extensively the role of CDK4/6 inhibitors. At this point in time, there are at least 8 large randomized studies that have looked at the addition of a CDK4/6 inhibitor to backbone endocrine therapy either in the first line or second line pretreated setting. These trials have used all 3 available agents and a diversity of endocrine backbone, but importantly and consistently there is a substantial improvement in hazard ratio across the board. Hazard ratio is .5 to .55 so adjusting a doubling in progression-free survival with the addition of the CDK4/6 inhibitor, and that has really become our standard of care for the majority of patients in the first-line or second-line setting.

We’ve also just in the past year seen some overall survival data from these agents, and again it’s suggesting that there may be an overall survival advantage from the use of CDK4/6 inhibitors, even more supporting the up-front use of these agents. The big question that’s come up though is, after CDK4/6 inhibitor, if the cancer is progressing, what do we give next, what are our next best strategies, should we be continuing on a CDK4/6 inhibitor like we do with trastuzumab for HER2-positive breast cancer or should we be switching to a different endocrine therapy with a new targeted partner and how can we best select that targeted partner? In terms of the idea of maintaining CDK4/6 inhibition, there are multiple studies ongoing which are trying to address this question. I’m fortunate to lead a study called PACE, which is a randomized study open throughout the United States in which patients who have progressed on a CDK4/6 inhibitor are then randomized to 1 of 3 arms, fulvestrant (Faslodex) alone, which can be standard of care in many patients, fulvestrant with the CDK4/6 inhibitor palbociclib or a triple combination of fulvestrant, palbociclib, and avelumab (Bavencio) which is an immunotherapy agent.  And this is based off of some strong preclinical data, and we’re actively accruing and we’re hoping to address this question.