MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer

Matthew P. Goetz, Masakazu Toi, Mario Campone, Olivier Trédan, Nawel Bourayou, Joohyuk Sohn, In Hae Park, Shani Paluch-Shimon, Jens Huober, Shin Cheh Chen, Luis Manso, Susana Barriga, Orit C. Freedman, Georgina Garnica Jaliffe, Tammy Forrester, Martin Frenzel, Ian C. Smith, Angelo Di Leo

Research output: Contribution to journalArticlepeer-review

502 Scopus citations


Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm and 44% in the placebo arm (P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1% v1.2%), diarrhea (9.5% v 1.2%), and leukopenia (7.6% v 0.6%). Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.

Original languageEnglish (US)
Pages (from-to)3638-3646
Number of pages9
JournalJournal of Clinical Oncology
Issue number32
StatePublished - Nov 10 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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