The FDA has approved abemaciclib for women with advanced or metastatic ER-positive, HER2-negative breast cancer whose disease has progressed on endocrine therapy. This is the third CDK4/6 inhibitor to get the agency's go-ahead in 2.5 years.

The FDA approved abemaciclib (Verzenio; Eli Lilly) in late September for women with advanced or metastatic ER-positive, HER2-negative breast cancer whose disease has progressed on endocrine therapy. The CDK4/6 inhibitor received the agency's go-ahead to be given alone or in combination with fulvestrant.

Following on the heels of palbociclib (Ibrance; Pfizer) and ribociclib (Kisqali; Novartis), abemaciclib is the third agent in this class to be greenlighted within the last 2.5 years—albeit as second-line therapy, whereas the other two can be given as part of initial endocrine-based treatment.

Data from two trials, MONARCH1 and MONARCH2, proved central to the FDA's decision. In the first, a single-arm study, the objective response rate (ORR) to abemaciclib among 132 patients was 19.7%, lasting for a median of 8.6 months. In the second trial, 669 patients were randomized 2:1 to receive abemaciclib plus fulvestrant or placebo plus fulvestrant. The median progression-free survival (PFS) in the abemaciclib cohort was 16.4 months, versus 9.3 months in the control group; among patients with measurable disease, the ORRs were 48.1% and 21.3%, respectively.

George Sledge, MD, of Stanford University Medical Center in Palo Alto, CA, observed that “this ORR is the highest recorded, to our knowledge, in an endocrine therapy–resistant population” when he reported MONARCH2's results during the 2017 American Society of Clinical Oncology Annual Meeting. Ingrid Mayer, MD, of Vanderbilt-Ingram Cancer Center in Nashville, TN, added that “the overall good quality of life, long duration of benefit, and delay in chemotherapy initiation are absolutely clear reasons” to incorporate CDK4/6 inhibitors at some point in patients with this breast cancer subtype.

More recently, abemaciclib has also shown strong first-line efficacy in advanced ER-positive, HER2-negative breast cancer, according to an interim analysis of the MONARCH3 trial presented during the ESMO 2017 Congress, the annual meeting of the European Society for Medical Oncology. The median PFS was not reached among patients randomly assigned to receive abemaciclib alongside letrozole, but was 14.7 months for those given placebo plus letrozole.

Overall, abemaciclib's approval “offers another tool in the breast oncologist's armamentarium,” notes C. Kent Osborne, MD, director of Baylor College of Medicine's Cancer Center in Houston, TX, “but how these three different CDK4/6 inhibitors will eventually fit in clinical practice will take more time and study.” –Alissa Poh