Abemaciclib Plus Fulvestrant in Patients With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Final Overall Survival Results From MONARCH 2

PURPOSE The MONARCH 2 study demonstrated statistically significant benefit in final progression-free survival (PFS) and interim overall survival (OS) with abemaciclib plus fulvestrant for cyclin-dependent kinase 4/6 inhibitor–naïve hormone receptor–positive, human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC) that progressed during endocrine therapy (ET). Here, we report final prespecified OS analyses and other secondary end points. METHODS Patients with hormone receptor–positive, HER2– ABC who had disease progression during ET were randomly assigned 2:1 to receive abemaciclib or placebo, plus fulvestrant. The primary end point was investigator-assessed PFS; key secondary end points included OS and safety, and chemotherapy-free survival was an exploratory end point. RESULTS With a median 80-month follow-up, a total of 440 OS events occurred (abemaciclib, 283; placebo, 157). Median OS was 45.8 and 37.3 months with abemaciclib and placebo, respectively (hazard ratio HR, 0.784 95% CI, 0.644 to 0.955). Although OS benefit was generally consistent across subgroups, a notable numerical benefit was observed in subgroups with poorer prognosis: visceral disease (HR, 0.643 95% CI, 0.499 to 0.829), primary resistance to ET (HR, 0.634 95% CI, 0.436 to 0.922), and progesterone receptor–negative status (HR, 0.623 95% CI, 0.405 to 0.959). Abemaciclib also delayed subsequent chemotherapy initiation (HR, 0.674 95% CI, 0.562 to 0.809), with substantial difference in yearly chemotherapy-free survival rates (3-year, 42.0% v 29.3%; 4-year, 37% v 18.6%, 5-year, 32.4% v 14.7%). No new safety signals or cumulative toxicities were identified with prolonged abemaciclib exposure. CONCLUSION These results further validate the clinical benefit previously demonstrated in MONARCH 2, reinforcing abemaciclib plus fulvestrant as an effective treatment option for patients with hormone receptor–positive, HER2– ABC who progressed after previous ET.