Hope Rugo, MD
The next wave of progress in hormone receptor (HR)-positive breast cancer treatment is likely to center around earlier introduction of CDK4/6 inhibitors, uncovering mechanisms of resistance through cell-free DNA (cfDNA), and developing novel pathway blockades like PI3K inhibitors, explained Hope S. Rugo, MD.
State of the Science Summit™ on Breast Cancer, Rugo, a professor of medicine and director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, discussed CDK4/6 inhibition in HR-positive breast cancer, mechanisms of resistance to these drugs, and other potential pathway blockades.
OncLive: What do we know about CDK4/6 inhibitors in HR-positive metastatic breast cancer?
We now have 3 CDK4/6 inhibitors: palbociclib, ribociclib, and abemaciclib that are approved in the first-, second-, or greaterline settings in combination with endocrine therapy. Abemaciclib is approved in later-line treatment after chemotherapy as a single agent.
We know that we can partner these drugs in postmenopausal patients and in premenopausal women on ovarian suppression. We know that it doesn’t appear to be safe to combine tamoxifen with ribociclib in the premenopausal population because you may enhance the QT effect of that drug. On the other hand, we know that fulvestrant (Faslodex) can be given safely with all 3 CDK4/6 inhibitors, even in the first-line setting based on the MONALEESA-3 trial.
Where is the field headed?
We know that progression-free survival (PFS) is essentially doubled with the addition of a CDK4/6 inhibitor. We will see the data from PALOMA-3 in terms of [overall] survival at the 2018 ESMO Congress. It will be really fascinating to understand the impact on survival and to learn if there’s a subpopulation of patients who benefit.
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