PracticeUpdate: What is the rationale of adding ribociclib to an aromatase inhibitor in the first-line setting for hormone-receptor positive breast cancer?
Dr. Tolaney: At ESMO this year, we saw some really exciting data come out from MONALEESA-2. I think most people are familiar with this study; this was a trial that had taken postmenopausal patients who had hormone receptor positive breast cancer and had randomized them in the first-line metastatic setting to receive an aromatase inhibitor with or without ribociclib. We know from previously presented data that adding ribociclib to an aromatase inhibitor did in fact double progression-free survival, but what we had been waiting on was overall survival data: really trying to understand if adding a CDK4/6 inhibitor to an aromatase inhibitor could not just improve progression-free survival, but if it could indeed improve overall survival.
What we saw at ESMO was, in fact, that adding ribociclib did extend overall survival, and in fact, it has extended it to be now over five years with a median OS that, again, exceeds five years. This, to me, is really exciting data, because it's the first time that we have seen overall survival data exceed five years at a median for hormone receptor positive breast cancer patients. I think this really shows that CDK4/6 inhibitors have shifted outcomes for this patient population.
PracticeUpdate: How are the study outcomes different from other trials with CDK4/6 inhibitors and what all outcomes are desired to confirm the efficacy of the treatment option?
Dr. Tolaney: This is the first study to report survival data for a CDK4/6 inhibitor in combination with an aromatase inhibitor. We've previously seen survival data with ribociclib from the MONALEESA-7 study, which was specific to pre-menopausal patients, which also showed an improvement in overall survival. We've also seen survival data from MONALEESA-3, which had looked at adding ribociclib to fulvestrant. We have not yet seen survival data from the other CDK4/6 inhibitors when they were added to an aromatase inhibitor. Specifically, we don't yet have overall survival data from PALOMA-2, which had looked at adding palbociclib to an aromatase inhibitor, and we don't yet have survival data from MONARCH 3, which had looked at adding abemaciclib to an aromatase inhibitor.
I think we're eagerly awaiting data from the other studies to know if adding CDK4/6 inhibition with abemaciclib or palbociclib to an AI will also extend overall survival. I think these data are really very important data, because, again, it does show that adding ribociclib to an AI is improving survival and, to me, really reinforces that CDK4/6 inhibition really needs to be first line standard of care for the vast majority of our metastatic hormone receptor-positive breast cancer patients.