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J Clin Oncol. 2017 Nov 10;35(32):3638-3646. doi: 10.1200/JCO.2017.75.6155. Epub 2017 Oct 2.

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer.

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Matthew P. Goetz, Mayo Clinic, Rochester, MN; Masakazu Toi, Kyoto University, Kyoto, Japan; Mario Campone, Institut de Cancerologie de l'Ouest, Angers Cedex; Olivier Trédan, Centre Léon Bérard, Lyon; Nawel Bourayou, Eli Lilly, Paris, France; Joohyuk Sohn, Yonsei Cancer Center, Seoul; In Hae Park, National Cancer Center, Goyangsi, South Korea; Shani Paluch-Shimon, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Jens Huober, University of Ulm, Ulm, Germany; Shin-Cheh Chen, Chang Gung University Medical College, Taipei, Taiwan; Luis Manso, Hospital Universitario 12 de Octubre; Susana Barriga, Eli Lilly, Madrid, Spain; Orit C. Freedman, Durham Regional Cancer Centre, Oshawa, Ontario, Canada; Georgina Garnica Jaliffe, Grupo Médico CAMINO S.C., Mexico City, Mexico; Tammy Forrester, Martin Frenzel, and Ian C. Smith, Eli Lilly, Indianapolis, IN; and Angelo Di Leo, Hospital of Prato, Prato, Italy.


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% v 1.2%), 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.

[Indexed for MEDLINE]

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