Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2− advanced breast cancer: final overall survival results of MONARCH 3

Highlights•This phase III trial evaluated abemaciclib + NSAI versus placebo + NSAI as initial therapy for HR+, HER2− ABC.•Addition of abemaciclib to an NSAI resulted in numerically longer OS; however, statistical significance was not reached.•Absolute improvement in median OS was clinically meaningful (ITT: 13.1 months; sVD: 14.9 months).•The previously demonstrated PFS benefit with the addition of abemaciclib was sustained (median improvement 14.3 months).•The addition of abemaciclib delayed subsequent receipt of chemotherapy (median improvement 16.1 months).AbstractBackgroundIn MONARCH 2, the addition of abemaciclib to fulvestrant significantly improved both progression-free survival (PFS) and overall survival (OS) in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) with disease progression on prior endocrine therapy. In MONARCH 3, the addition of abemaciclib to a nonsteroidal aromatase inhibitor (NSAI) as initial therapy for HR+, HER2− ABC significantly improved PFS. Here, we present the prespecified final OS results for MONARCH 3.Patients and methodsMONARCH 3 is a randomized, double-blind, phase III study of abemaciclib plus NSAI (anastrozole or letrozole) versus placebo plus NSAI in postmenopausal women with HR+, HER2− ABC without prior systemic therapy in the advanced setting. The primary objective was investigator-assessed PFS; OS was a gated secondary endpoint, and chemotherapy-free survival was an exploratory endpoint.ResultsA total of 493 women were randomized 2 : 1 to receive abemaciclib plus NSAI (n = 328) or placebo plus NSAI (n = 165). After a median follow-up of 8.1 years, there were 198 OS events (60.4%) in the abemaciclib arm and 116 (70.3%) in the placebo arm (hazard ratio, 0.804; 95% confidence interval 0.637-1.015; P = 0.0664, non-significant). Median OS was 66.8 versus 53.7 months for abemaciclib versus placebo. In the subgroup with visceral disease, there were 113 OS events (65.3%) in the abemaciclib arm and 65 (72.2%) in the placebo arm (hazard ratio, 0.758; 95% confidence interval 0.558-1.030; P = 0.0757, non-significant). Median OS was 63.7 months versus 48.8 months for abemaciclib versus placebo. The previously demonstrated PFS benefit was sustained, and chemotherapy-free survival numerically improved with the addition of abemaciclib. No new safety signals were observed.ConclusionsAbemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS (intent-to-treat population: 13.1 months; subgroup with visceral disease: 14.9 months) in patients with HR+ HER2− ABC; however, statistical significance was not reached.