Multinational phase 3 trial of abemaciclib plus fulvestrant for HR+, HER2- advanced breast cancer following progression on CDK4/6 inhibitor plus ET: overall survival analysis

The multinational phase 3 postMONARCH trial demonstrated a significant improvement in progression-free survival (PFS) with abemaciclib plus fulvestrant versus placebo plus fulvestrant among participants with HR-positive, HER2-negative advanced breast cancer (HR+ HER2- aBC) after disease progression on CDK4/6i plus endocrine therapy (ET). Prespecified overall survival (OS) analysis, after 200 OS events, has now been reported. Participants were randomized 1:1 to abemaciclib plus fulvestrant (n=182) or placebo plus fulvestrant (n=186). At data cutoff, median follow-up was approximately 37 months. A total of 90 (50%) OS events were observed in the abemaciclib plus fulvestrant group, compared with 110 (59%) in the placebo plus fulvestrant group. Median overall survival was 32.1 months with abemaciclib plus fulvestrant versus 24.6 months with placebo plus fulvestrant (HR 0.80; 95% CI 0.60-1.06; boundary for significance not reached). OS differences were consistent across subgroups. Updated PFS was consistent with the primary analysis. Time to second progression and chemotherapy-free survival also favored abemaciclib plus fulvestrant. Safety was consistent with the established abemaciclib profile. The authors conclude that abemaciclib plus fulvestrant resulted in numerically longer median OS versus placebo plus fulvestrant, although statistical significance was not reached. The totality of evidence supports consideration of abemaciclib-based treatment for patients with HR+ HER2- aBC after disease progression of CDK4/6i plus ET.