MONARCH 2: subgroup analysis of patients receiving abemaciclib plus fulvestrant as first-line and second-line therapy for HR+, HER2- advanced breast cancer.

Abstract

PURPOSE\nIn MONARCH 2, abemaciclib plus fulvestrant significantly prolonged progression-free survival (PFS) and overall survival (OS) versus placebo plus fulvestrant in patients with hormone receptor positive (HR+), HER2- advanced breast cancer. This exploratory analysis assessed the efficacy of abemaciclib plus fulvestrant across subgroups of patients receiving study therapy as first- or second-line treatment for metastatic disease.\n\n\nEXPERIMENTAL DESIGN\nImprovements were estimated using Cox models, and a test of interactions of subgroups with treatment was performed.\n\n\nRESULTS\nThe benefit in PFS (first-line, HR=0.57 [95% CI: 0.45-0.73]; second-line, HR=0.48 [95% CI: 0.36-0.64]) and OS (first-line, HR=0.85 [95% CI: 0.64-1.14]; second-line, HR=0.66 [95% CI: 0.46-0.94]) was observed across both subgroups, consistent with the intent-to-treat (ITT) population. In first-line patients (abemaciclib arm, n=265; placebo arm, n=133), the numerically largest effect on PFS and OS was observed in patients with primary resistance to endocrine therapy (ET) (PFS, HR=0.40 [95% CI: 0.26-0.63]; OS, HR=0.58 [95% CI: 0.35-0.97]) and visceral disease (PFS, HR=0.54 [95% CI: 0.39-0.73]; OS, HR=0.82 [95% CI: 0.58-1.20]). In second-line patients (abemaciclib arm, n=170; placebo arm, n=86), a numerical benefit in PFS and OS was observed across primary and secondary ET resistance, with numerically more pronounced effects observed in patients with visceral disease (PFS, HR=0.39 [CI: 0.27-0.57]; OS, HR=0.51 [95% CI: 0.33-0.81]). Prolongation of time to second disease progression, time to chemotherapy, and chemotherapy‑free survival was observed in both subgroups.\n\n\nCONCLUSIONS\nConsistent with the ITT population, a benefit in PFS and OS was observed across the first- and second-line subgroups in MONARCH 2.