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:

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.

• Authors: Patrick Neven, Stephen R D 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 C Hurt, Antonio Llombart-Cussac, George W Sledge
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 27 Issue 21 Pg. 5801-5809 (11 01 2021) ISSN: 1557-3265 [Electronic] United States
• PMID: 34376533 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2021 American Association for Cancer Research.

Chemical References

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

Topics

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