Dr. Tolaney: So, at ESMO, we saw data from monarcHER. This was a randomized phase II study that looked at the use of CDK4/6 inhibition in patients with metastatic HER2-positive breast cancer. So, while CDK4/6 inhibitors are standard in ER-positive HER2-negative disease, there's a lot of preclinical data to suggest that these agents can also work in ER-positive HER2-positive breast cancers. And so, monarcHER was really designed to assess the efficacy of CDK4/6 inhibition with anti-HER2 therapy in pretreated metastatic HER2-positive breast cancer. And so, in this design, patients who had ER-positive, HER2-positive disease that had progressed on at least two prior lines of systemic therapy in the metastatic setting were randomized to get fulvestrant with abemaciclib with trastuzumab, or to get abemaciclib with trastuzumab, or to get chemotherapy, of physician's choice, with trastuzumab.
And we'd originally seen data come out with regards to progression-free survival where we saw that the triplet combination of fulvestrant, abemaciclib, and trastuzumab was associated with an improvement in PFS compared to the control of chemo-trastuzumab, with a difference between the two arms of about 2.6 months. So, really suggesting that a non-chemotherapy-containing regimen was doing better than chemotherapy in pretreated patients.
Striking improvement in overall survival with abemaciclib
But now we actually saw data come out with regards to overall survival, where we actually saw that the two abemaciclib-containing arms had improved overall survival that was not statistically significant but was a trend when compared to the chemotherapy-trastuzumab arm. And so, the difference between the abemaciclib arms and the chemotherapy arm was actually about 10 months. So, going from about 20 months to 30 months; so, really quite a striking improvement in overall survival. And to me this is exciting because it really suggests that using a non-chemotherapy-containing regimen can improve outcomes for our ER-positive, HER2-positive patients and so I think can be used selectively in patients who are trying to omit chemotherapy in a pretreated ER-positive, HER2-positive setting.