MONARCH 3: Interim overall survival (OS) results of abemaciclib plus a nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+, HER2-advanced breast cancer (ABC)

Abstract

Background MONARCH 2 led to abemaciclib + fulvestrant approval in pts with HR+, HER2- ABC with disease progression on prior endocrine therapy and demonstrated significant OS benefit. MONARCH 3 led to abemaciclib + NSAI approval as initial therapy in postmenopausal pts with HR+, HER2- ABC with significant improvement in progression-free survival (PFS). Here we report the second interim analysis (IA2) OS results for MONARCH 3, an analysis included in the European Product Label by request of EMA.

Methods MONARCH 3 is a 2:1 randomized, double-blind, placebo-controlled Phase 3 study of NSAI +/- abemaciclib. Detailed study information, including the primary endpoint of PFS are published (Goetz, JCO 2017). OS is a key secondary endpoint and this prespecified OS IA2 (data cut 2 Jul 2021) was scheduled after ∼252 events in the ITT population (80% of planned events for final OS analysis), using a stratified log-rank test and applying a pre-defined error spending strategy to assess significance in both the ITT and the subgroup with visceral disease (sVD).

Results 493 pts were randomized to receive NSAI + abemaciclib (n=328) or placebo (n=165). At IA2, with 70.2 months median follow-up, in the ITT the median OS (mOS) was 67.1 months for abemaciclib + NSAI vs 54.5 months for placebo + NSAI (HR=0.754, 95% CI: 0.584-0.974, 2-sided p=0.0301). In sVD, the mOS was 65.1 months for abemaciclib + NSAI vs 48.8 months for placebo + NSAI (HR=0.708, 95% CI: 0.508-0.985; 2-sided p=0.0392). According to the alpha spending procedure, the critical boundaries for declaring significance in both groups were not met for IA2. Follow-up is ongoing for final OS analysis (expected 2023). Safety data were consistent with the known profile of abemaciclib.

Conclusions In the second interim prespecified overall survival analysis from MONARCH 3, longer OS was observed in both the ITT and sVD (an increase in the median OS by >12 months with the addition of abemaciclib to NSAI), however neither met the threshold for formal statistical significance according to the alpha spend procedure. Final OS analysis is planned when at least 315 OS events in ITT and 189 in sVD are observed.

Clinical trial identification NCT02246621