Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HRD, HER2L advanced breast cancer: final overall survival results of MONARCH 3

Abstract

Background: In MONARCH 2, the addition of abemaciclib to fulvestrant significantly fi cantly 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 fi cantly improved PFS. Here, we present the prespecified fi ed fi nal OS results for MONARCH 3. Patients and methods: MONARCH 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. Results: A 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 fi dence interval 0.637-1.015; P = 0.0664, non-significant). fi cant). 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 fi dence interval 0.558-1.030; P = 0.0757, non-significant). fi cant). Median OS was 63.7 months versus 48.8 months for abemaciclib versus placebo. The previously demonstrated PFS benefit fi t was sustained, and chemotherapy-free survival numerically improved with the addition of abemaciclib. No new safety signals were observed. Conclusions: Abemaciclib 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 fi cance was not reached.