Purpose
Abemaciclib, a
cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with
fulvestrant in women with
hormone receptor (HR)-positive,
human epidermal growth factor receptor 2 (HER2)-negative advanced
breast cancer previously treated with endocrine
therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of
abemaciclib or placebo plus a nonsteroidal
aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced
breast cancer who had no prior systemic
therapy in the advanced setting. Patients received
abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg
anastrozole or 2.5 mg
letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the
abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the
abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the
abemaciclib arm and 44% in the placebo arm ( P = .004). In the
abemaciclib arm,
diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing
abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were
neutropenia (21.1% v 1.2%),
diarrhea (9.5% v 1.2%), and
leukopenia (7.6% v 0.6%). Conclusion
Abemaciclib plus a nonsteroidal
aromatase inhibitor was effective as initial
therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced
breast cancer.