Disproportionality Analysis of Abemaciclib in the FDA Adverse Event Reporting System: A Real-World Post-Marketing Pharmacovigilance Assessment

Abstract

Background and objective: Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Because of the limitations of clinical trials, which are not representative of large real-world populations, rare events and long-term safety concerns cannot be detected. The current study aimed to evaluate the adverse events of abemaciclib through data mining of the Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods: Reporting odds ratio and Bayesian confidence propagation neural network of information components were used to quantify the adverse event signals of abemaciclib from the third quarter of 2017 to the first quarter of 2022. Serious and non-serious cases were compared using the Mann-Whitney U test or Chi-squared test, and clinical priority was assigned to signals by scoring (range 0-10 points) five features using a rating scale.

Results: A total of 6125 reports of abemaciclib as the "primary suspected" and 72 significant adverse events of abemaciclib were identified. Common adverse events, such as diarrhea, neutropenia, alanine transaminase, aspartate transaminase, and serum creatinine increases, and other adverse events, including thrombosis, deep vein thrombosis, pulmonary embolism, interstitial lung disease, and pneumonitis were of high concern. Of note, 17 preferred terms were classified as unexpected adverse events that uncovered in the label. In addition, 1, 26, and 45 adverse events were identified as strong, moderate, and weak clinical priorities. The median time to onset for strong, moderate, and weak clinical priority signals was 49, 22, and 28 days, respectively. All of the disproportionality signals had early failure type features, suggesting that adverse events of abemaciclib gradually decreased over time.

Conclusions: The discovery of disproportionality signals could potentially prompt improved awareness of toxicities for abemaciclib, and the results of time to onset, serious and non-serious reports, and clinical priority analyses provided some supporting evidence for clinicians to manage adverse events.