Management of Abemaciclib‐Associated Adverse Events in Patients with Hormone Receptor‐Positive, Human Epidermal Growth Factor Receptor 2‐Negative Advanced Breast Cancer: Safety Analysis of MONARCH 2 and MONARCH 3

Background Abemaciclib demonstrated efficacy in hormone receptor‐positive, human epidermal growth factor receptor 2‐negative advanced breast cancer. Here we provide a comprehensive summary of the most common adverse events (AEs), their management, and whether AEs or dose reductions influenced progression‐free survival (PFS), in the MONARCH 2 and 3 trials. Materials and Methods Incidence of the most clinically relevant AEs, management, and outcomes were summarized. Time‐dependent covariate analyses examined the impact of dose reductions on PFS. PFS was estimated for patients with and without early onset of diarrhea or neutropenia. Results The most frequently reported AE was diarrhea, with clinically significant diarrhea (grade ≥2) reported for 42.8% of patients taking abemaciclib. Median time to onset was 1 week, and duration ranged from 6 to 12 days, depending on grade and study. Diarrhea was adequately managed by antidiarrheal medication (72.8%), dose omissions (17.3%), and reductions (16.7%). The highest rates of grade ≥2 diarrhea were observed in the first cycles and decreased in subsequent cycles. Neutropenia (grade ≥3) occurred in 25.4% of abemaciclib‐treated patients. Neutropenia resolved with dose omissions (16.8%) and/or dose reductions (11.2%). Incidence of febrile neutropenia (0.7%) or other relevant grade ≥3 hematological events (