MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer

By S. Johnston, Miguel Martín, A. Di Leo, S. Im, A. Awada, T. Forrester, Martin Frenzel, M. C. Hardebeck, J. Cox, S. Barriga and 3 more. npj Breast Cancer, 2019

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At the MONARCH 3 interim analysis, abemaciclib plus a nonsteroidal aromatase inhibitor (AI) significantly improved progression-free survival (PFS) and objective response rate (ORR) with a tolerable safety profile as initial treatment for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC). MONARCH 3 is a randomized, phase III, double-blind study of abemaciclib/placebo (150 mg twice daily, continuous) plus nonsteroidal AI (1 mg anastrozole or 2.5 mg letrozole, daily). A total of 493 postmenopausal women with HR+, HER2− ABC with no prior systemic therapy in this setting were enrolled. The primary endpoint was investigator-assessed PFS (final analysis after 240 events); other endpoints included response and safety evaluations. Here we analyze the final PFS data and update secondary endpoints. The abemaciclib arm had a significantly longer median PFS than the placebo arm (28.18 versus 14.76 months; hazard ratio [95% confidence interval], 0.540 [0.418–0.698]; p = .000002). The ORR was 61.0% in the abemaciclib arm versus 45.5% in the placebo arm (measurable disease, p = .003). The median duration of response was longer in the abemaciclib arm (27.39 months) compared to the placebo arm (17.46 months). The safety profile was consistent with previous reports. The most frequent grade ≥ 3 adverse events in the abemaciclib versus placebo arms were neutropenia (23.9% versus 1.2%), diarrhea (9.5% versus 1.2%), and leukopenia (8.6% versus 0.6%). Abemaciclib plus a nonsteroidal AI was an effective initial treatment with an acceptable safety profile for HR+, HER2− ABC. Patients with the most common form of breast cancer stand to benefit from taking a drug that blocks two cell cycle–regulating proteins in addition to hormonal therapy. In a phase III clinical trial, Stephen Johnston from the Royal Marsden NHS Foundation Trust
in London, UK, and colleagues randomly gave 493 postmenopausal women with HR+/HER2− metastatic breast cancer a nonsteroidal aromatase inhibitor plus either a placebo or a drug called abemaciclib, a targeted inhibitor of CDK4 and CDK6. A planned interim analysis previously showed that abemaciclib was safe and effective. Johnson’s team now reports that abemaciclib nearly doubled the time women live without disease recurrence, from 15 months on placebo to 28 months on the drug. Additionally, responses were more common and lasted longer among women who received both abemaciclib and the hormonal therapy.

Subfields: Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/c159668b9470c9a75ba2c701ff4a3403f305b644

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