Purpose
The phase 2 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 2 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%).
Conclusion
In this poor-prognosis, heavily pre-treated population with refractory HR+/HER2- metastatic breast cancer, continuous dosing of single agent abemaciciclib was well tolerated and exhibited promising clinical activity.