Overall survival from the phase III postMONARCH trial of abemaciclib plus fulvestrant versus placebo plus fulvestrant for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy.

Abstract

The phase III postMONARCH trial demonstrated a statistically significant improvement in progression-free survival (PFS) with abemaciclib plus fulvestrant versus placebo plus fulvestrant in participants with HR+, HER2- advanced breast cancer (ABC) after disease progression on prior CDK4/6i plus endocrine therapy (ET). Here we report the prespecified final overall survival (OS) analysis. Eligible patients had disease progression on a CDK4/6i plus aromatase inhibitor as initial therapy for ABC or recurrence on or after adjuvant CDK4/6i plus ET. Participants were randomly assigned 1:1 to receive abemaciclib plus fulvestrant or placebo plus fulvestrant. The final OS analysis was pre-specified at 200 OS events (HR boundary 0.753). Time-to-event analyses used the Kaplan-Meier method, and stratified Cox models were used to estimate the HR and 95% confidence intervals (CI). A total of 368 participants were randomly assigned 1:1 to abemaciclib plus fulvestrant (n = 182) or placebo plus fulvestrant (n = 186). At data cutoff, median follow-up was approximately 37 months; 200 OS events were observed (90 [50%] vs 110 [59%]). Median OS was 32.1 months with abemaciclib plus fulvestrant versus 24.6 months with placebo plus fulvestrant (HR, 0.80 [95% CI, 0.60 to 1.06]; P = 0.11, boundary for significance not reached). OS differences were consistent across subgroups. Updated PFS was consistent with the primary analysis (HR, 0.78 [95% CI, 0.62 to 0.99]; nominal P = 0.039). Time to second progression and chemotherapy-free survival also favored abemaciclib plus fulvestrant. Safety was consistent with the established abemaciclib profile with no new signals identified. Abemaciclib plus fulvestrant resulted in numerically longer median OS versus placebo plus fulvestrant, though statistical significance was not reached. The totality of evidence supports consideration of abemaciclib-based treatment for patients with HR+, HER2- ABC after disease progression on prior CDK4/6i plus ET. NCT05169567.