MONARCH 2: Subgroup Analysis of Patients Receiving Abemaciclib Plus Fulvestrant as First-Line and Second-Line Therapy for HR+, HER2−-Advanced Breast Cancer
Patrick Neven, Stephen Johnston, Masakazu Toi, Joohyuk Sohn, Kenichi Inoue, Xavier Pivot, Olga Burdaeva, Meena Okera, Norikazu Masuda, Peter A. Kaufman, Han Koh, Eva‐Maria Grischke, PierFranco Conte, Yi Lu, Nadine Haddad, Karla Hurt, Antonio Llombart‐Cussac, George W. Sledge
Abstract
Abstract Purpose: In 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. Patients and Methods: Improvements were estimated using Cox models, and a test of interactions of subgroups with treatment was performed. Results: The benefit in PFS [first-line, HR, 0.57; 95% confidence interval (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; 95% 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. Conclusions: Consistent with the ITT population, a benefit in PFS and OS was observed across the first- and second-line subgroups in MONARCH 2.