• George W Sledge, Masakazu Toi, Patrick Neven, Joohyuk Sohn, Kenichi Inoue, Xavier Pivot, Olga Burdaeva, Meena Okera, Norikazu Masuda, Peter A Kaufman, Han Koh, Eva-Maria Grischke, Martin Frenzel, Yong Lin, Susana Barriga, Ian C Smith, Nawel Bourayou, and Antonio Llombart-Cussac.
• George W. Sledge Jr., Stanford University, Stanford; Han Koh, Kaiser Permanente Medical Group, Bellflower, CA; Masakazu Toi, Kyoto University; Kenichi Inoue, Saitama Cancer Center, Saitama; Norikazu Masuda, Osaka National Hospital, Osaka, Japan; Patrick Neven, Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg, Leuven, Belgium; Joohyuk Sohn, Yonsei Cancer Center, Seoul, Korea; Xavier Pivot, CHU de Besancon Hopital Jean Minjoz, Besancon Cedex; Nawel Bourayou, Eli Lilly, Paris, France; Olga Burdaeva, Arkhangelsk Regional Clinical Oncology Dispensary, Arkhangelsk, Russian Federation; Meena Okera, Adelaide Cancer Centre, Adelaide, Australia; Peter A. Kaufman, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Eva-Maria Grischke, Universitätsklinikum Tübingen Frauenklinik, Tübingen, Germany; Martin Frenzel, Yong Lin, and Ian C. Smith, Eli Lilly, Indianapolis, IN; Susana Barriga, Eli Lilly, Madrid; and Antonio Llombart-Cussac, Hospital Arnau Vilanova, Valencia, Spain.
• J. Clin. Oncol. 2017 Sep 1; 35 (25): 2875-2884.

AbstractPurpose MONARCH 2 ( ClinicalTrials.gov identifier: NCT02107703) compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, plus fulvestrant with fulvestrant alone in patients with advanced breast cancer (ABC). Patients and Methods MONARCH 2 was a global, double-blind, phase III study of women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who had progressed while receiving neoadjuvant or adjuvant endocrine therapy (ET), ≤ 12 months from the end of adjuvant ET, or while receiving first-line ET for metastatic disease. Patients were randomly assigned 2:1 to receive abemaciclib or placebo (150 mg twice daily) on a continuous schedule and fulvestrant (500 mg, per label). The primary end point was investigator-assessed progression-free survival (PFS), and key secondary end points included overall survival, objective response rate (ORR), duration of response, clinical benefit rate, quality of life, and safety. Results Between August 2014 and December 2015, 669 patients were randomly assigned to receive abemaciclib plus fulvestrant (n = 446) or placebo plus fulvestrant (n = 223). Abemaciclib plus fulvestrant significantly extended PFS versus fulvestrant alone (median, 16.4 v 9.3 months; hazard ratio, 0.553; 95% CI, 0.449 to 0.681; P < .001). In patients with measurable disease, abemaciclib plus fulvestrant achieved an ORR of 48.1% (95% CI, 42.6% to 53.6%) compared with 21.3% (95% CI, 15.1% to 27.6%) in the control arm. The most common adverse events in the abemaciclib versus placebo arms were diarrhea (86.4% v 24.7%), neutropenia (46.0% v 4.0%), nausea (45.1% v 22.9%), and fatigue (39.9% v 26.9%). Conclusions Abemaciclib at 150 mg twice daily plus fulvestrant was effective, significantly improving PFS and ORR and demonstrating a tolerable safety profile in women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who progressed while receiving ET.

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