MONARCH 2: Subgroup Analysis of Patients Receiving Abemaciclib Plus Fulvestrant as First-Line and Second-Line Therapy for HR+, HER2--Advanced Breast Cancer

Clin Cancer Res. 2021 Nov 1;27(21):5801-5809. doi: 10.1158/1078-0432.CCR-20-4685. Epub 2021 Aug 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines / administration & dosage*
  • Antineoplastic Agents, Hormonal / administration & dosage*
  • Benzimidazoles / administration & dosage*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Drug Combinations
  • Female
  • Fulvestrant / administration & dosage*
  • Humans
  • Neoplasm Staging
  • Progression-Free Survival
  • Receptor, ErbB-2 / analysis
  • Treatment Outcome

Substances

  • Aminopyridines
  • Antineoplastic Agents, Hormonal
  • Benzimidazoles
  • Drug Combinations
  • Fulvestrant
  • abemaciclib
  • Receptor, ErbB-2