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

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.

Figure 1

a. The best percent change in tumor size from baseline is plotted for each patient who had an available assessment b. Time on treatment with abemaciclib is plotted for each patient treated in the MONARCH 1 study (N=132). The colors in a and b represent response status per RECIST v1.1 and each bar in a and b represents one patient.

Figure 2

Analysis of Adverse Event of Diarrhea. Time on treatment (in days) is presented for each patient (N=132). Each bar represents one patient and the length of the bar represents the duration on treatment. The start and end of treatment emergent adverse events of diarrhea while on treatment are color-coded by grade.