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MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer

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

abstract 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.
   
citation Goetz M P, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park I H, Trédan O, Chen S C, Manso L, Freedman O C, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith I C, Bourayou N, Di Leo A. MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. J Clin Oncol 2017; 35:3638-3646.
   
type journal paper/review (English)
date of publishing 02-10-2017
journal title J Clin Oncol (35/32)
ISSN electronic 1527-7755
pages 3638-3646
PubMed 28968163
DOI 10.1200/JCO.2017.75.6155