CDK4/6 Inhibitors for Hormone-Driven Breast Cancer - Episode 19

HR+ Breast Cancer: Pooled Analysis From MONARCH 2 and 3


Joyce O’Shaughnessy, MD: The MONARCH 2 trial was fulvestrant with or without abemaciclib for patients whose diseases had progressed on an aromatase inhibitor [AI]. MONARCH 3 is a first-line trial of a nonsteroidal AI with or without abemaciclib. Both of the trials, of course, were positive, and the data from both were pooled to look at more favorable versus more concerning patient subgroups. It’s really interesting. First of all, every single subgroup of patients with metastatic breast cancer benefits from abemaciclib, as we have seen with all of the CDK4/6 [cyclin-dependent kinases 4 and 6] inhibitors. There isn’t a subset of patients, even the most endocrine therapy-sensitive, that doesn’t benefit additionally from the abemaciclib. But what’s interesting is that if you look across all the prognostic subsets, the patients did almost equally well in the abemaciclib arm.

Where it varies is how well they did with endocrine therapy alone, whether it be the nonsteroidal AI or fulvestrant. Women with more endocrine therapy-sensitive breast cancer did better with endocrine therapy. They did better yet with abemaciclib, but the difference isn’t so marked. Women with more concerning clinical characteristics did just as well with the abemaciclib as if they didn’t have concerning clinical characteristics, but they did much less well with the endocrine therapy. So, the differential benefit is much greater there from abemaciclib.

The concerning characteristics were really quite consistent with the picture we would expect for patients who have less endocrine therapy-sensitive disease. Patients with liver metastasis were particularly striking. Women with a shorter treatment-free interval—meaning their disease recurred either on endocrine therapy or within 3 years of stopping their adjuvant endocrine therapy, so women with a fast or a natural history that denotes more aggressive, highly proliferative disease—so women with grade 3 disease, also showed a greater differential benefit with abemaciclib compared to those with grade 1/2 disease. Women with progesterone receptor-negative breast cancer, which tends to be more highly proliferative, higher grade disease, had a greater differential benefit from abemaciclib. They had liver metastasis, shorter treatment-free intervals, higher grade disease, and progesterone receptor-negative disease. Women with bone-only disease, lower grade disease, and longer treatment-free intervals also benefitted from abemaciclib, just not so strikingly in a differential way.

Transcript Edited for Clarity