A real-world drug safety surveillance study from the FAERS database of breast cancer patients receiving abemaciclib alone and plus letrozole

Abemaciclib in combination with letrozole is considered a crucial treatment regimen for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) breast cancer. This study aims to monitor and identify adverse events (AEs) associated with this combination therapy to enhance patient safety and provide evidence-based recommendations for the appropriate use of these drugs. We collected data on adverse drug reactions (ADRs) related to breast cancer patients receiving either abemaciclib monotherapy or its combination with letrozole from the FDA Adverse Event Reporting System (FAERS) database between the first quarter of 2014 and the fourth quarter of 2024. ADR signal detection was conducted using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) methods. A total of 6,649 and 750 AE cases were collected for patients receiving abemaciclib monotherapy and its combination with letrozole, respectively. Using four signal detection techniques, we identified 42 and 28 distinct AEs, involving 15 and 11 different system organ class (SOC) categories, respectively. The most common AEs associated with abemaciclib were diarrhea, dehydration, and myelosuppression. In the combination therapy group, the most frequently reported AEs were diarrhea, interstitial lung disease, and acute kidney injury (AKI). Additionally, we observed a higher incidence of abnormal liver function in the combination therapy group, with a detected signal for hepatocellular necrosis. The United States reported the highest number of AEs, followed by Japan, China, France, and Italy. The median onset time of AEs associated with abemaciclib monotherapy and its combination with letrozole was 30 days (interquartile range [IQR]: 11–115 days) and 35 days (IQR: 14–109 days), respectively. This study provides novel insights into the monitoring and management of ADRs in breast cancer patients receiving abemaciclib monotherapy or in combination with letrozole.