MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer

• Published in: Journal of clinical oncology Vol. 35; no. 32; pp. 3638 - 3646
• Main Authors: Goetz, Matthew P., Toi, Masakazu, Campone, Mario, Sohn, Joohyuk, Paluch-Shimon, Shani, Huober, Jens, Park, In Hae, Trédan, Olivier, Chen, Shin-Cheh, Manso, Luis, Freedman, Orit C., Garnica Jaliffe, Georgina, Forrester, Tammy, Frenzel, Martin, Barriga, Susana, Smith, Ian C., Bourayou, Nawel, Di Leo, Angelo
• Format: Journal Article
• Language: English
• Published: United States 10.11.2017
• Subjects: Adult; Aged; Aged, 80 and over; Aminopyridines - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Aromatase Inhibitors - administration & dosage; Benzimidazoles - administration & dosage; Biomarkers, Tumor; Breast Neoplasms - drug therapy; Double-Blind Method; Female; Humans; Middle Aged; Nitriles - administration & dosage; Postmenopause; Receptor, ErbB-2; Survival Rate; Treatment Outcome; Triazoles - administration & dosage
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2017.75.6155

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.