MONARCH 1, A Phase II Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, as a Single Agent, in Patients with Refractory HR+/HER2− Metastatic Breast Cancer

TLDR

The MONARCH 1 phase II study evaluated the single‑agent activity and safety of abemaciclib in women with refractory hormone‑receptor positive, HER2‑negative metastatic breast cancer. Eligible patients had progressed after endocrine therapy and 1–2 chemotherapy lines and received 200 mg abemaciclib orally every 12 hours continuously until progression or unacceptable toxicity, with the primary endpoint being investigator‑assessed objective response rate and secondary endpoints including clinical benefit rate, progression‑free survival, and overall survival. The study reported a 19.7 % objective response rate, 42.4 % clinical benefit rate, median progression‑free survival of 6.0 months, median overall survival of 17.7 months, and common grade ≥ 1 adverse events of diarrhea, fatigue, and nausea, with only 7.6 % discontinuations due to toxicity. Clin Cancer Res 23(17):5218‑24; ©2017 AACR.

Abstract

Purpose: The phase II MONARCH 1 study was designed to evaluate the single-agent activity and adverse event (AE) profile of abemaciclib, a selective inhibitor of CDK4 and CDK6, in women with refractory hormone receptor-positive (HR+), HER2- metastatic breast cancer (MBC).Experimental Design: MONARCH 1 was a phase II single-arm open-label study. Women with HR+/HER2- MBC who had progressed on or after prior endocrine therapy and had 1 or 2 chemotherapy regimens in the metastatic setting were eligible. Abemaciclib 200 mg was administered orally on a continuous schedule every 12 hours until disease progression or unacceptable toxicity. The primary objective of MONARCH 1 was investigator-assessed objective response rate (ORR). Other endpoints included clinical benefit rate, progression-free survival (PFS), and overall survival (OS).Results: Patients (n = 132) had a median of 3 (range, 1-8) lines of prior systemic therapy in the metastatic setting, 90.2% had visceral disease, and 50.8% had ≥3 metastatic sites. At the 12-month final analysis, the primary objective of confirmed objective response rate was 19.7% (95% CI, 13.3-27.5; 15% not excluded); clinical benefit rate (CR+PR+SD≥6 months) was 42.4%, median progression-free survival was 6.0 months, and median overall survival was 17.7 months. The most common treatment-emergent AEs of any grade were diarrhea, fatigue, and nausea; discontinuations due to AEs were infrequent (7.6%).Conclusions: In this poor-prognosis, heavily pretreated population with refractory HR+/HER2- metastatic breast cancer, continuous dosing of single-agent abemaciciclib was well tolerated and exhibited promising clinical activity. Clin Cancer Res; 23(17); 5218-24. ©2017 AACR.