Abemaciclib—an oral, selective inhibitor of CDK4 and CDK6—demonstrated single-agent activity in a phase I trial of patients with refractory hormone-receptor positive (HR+) metastatic breast cancer (mBC), with some tumor responses occurring after at least 8 months of treatment. The phase II, single-arm MONARCH1 study evaluated the safety and efficacy of abemaciclib monotherapy in women with HR+/hormone estrogen receptor 2 negative (HER2−) mBC who have progressed on or after endocrine therapy and chemotherapy. The researchers presented the study at the ASCO Annual Meeting.

Patients were eligible for study inclusion if they had 

  • An Eastern Cooperative Oncology Group performance status of 0−1 
  • No central nervous system metastases 
  • Received at least one but not more than two lines of chemotherapy in the metastatic setting. 

A total of 132 patients received abemaciclib 200 mg administered orally on a continuous schedule every 12 hours until disease progression. The median patient age was 58 years (range = 36−89 years), 90.2% had visceral disease, and 85.6% had at least two metastatic sites. Patients with advanced disease had a median of three prior lines of therapy, including two lines of chemotherapy. 

An interim analysis was conducted at eight months, and 35.6% of patients had received at least eight cycles of therapy. The objective response rate was 17.4%, whereas the clinical benefit rate (including complete response, partial response, and stable disease occurring for at least six months) was 42.4% and the median progression-free survival was 5.7 months. 

Twenty-two patients continued to receive abemaciclib after the eight-month interim analysis, 13 of whom had responded and 9 who had stable disease. 

The most common treatment-related adverse events (AEs) were diarrhea, fatigue, nausea, decreased appetite, and abdominal pain. Treatment discontinuations related to AEs occurred in 6.8% of patients. 

The researchers concluded, “Abemaciclib induces objective tumor responses as a monotherapy in patients with refractory HR+/HER2− mBC following multiple prior therapies. Treatment was well tolerated, allowing prolonged exposure to therapy.”