Adverse events related to abiraterone and enzalutamide treatment. analysis of the EudraVigilance database and meta-analysis of registrational phase III studies

Background: Data from clinical trials do not always provide adequate information to judge the impact of new treatments when used in a real-world setting. The aim of our study was to analyze adverse events (AEs) associated with enzalutamide (ENZ) and abiraterone (ABI) using real-life data from the EudraVigilance (EV) database. Methods: The EV database is the system for managing and analyzing information on suspected adverse reactions to medicines, which have been authorized or are being studied in clinical trials in the European Economic Area. We recorded the number of AEs for ABI and ENZ per category and severity from January 2013 to January 2019. In addition, we recorded AEs per age group. A meta-analysis of AEs reported in registrational phase III studies (AFFIRM, PREVAIL, COU-AA) was performed. Results: The number of individual cases identified in EV database was 13,562 for ABI and 40,599 for ENZ. Over 90% of the reported AEs were defined as serious for both drugs. Older patients (>85 years and 65–85 years) treated with ABI or ENZ are at increased risk of cardiac, infectious, metabolic, and respiratory disorders when compared with younger patients (<65). According to registrational phase III studies, the most frequent AEs in patients treated with ABI are hepatobiliary disorders, while the most frequent AEs in patients treated with ENZ are psychiatric and vascular disorders. Several AEs present in the EV database are not reported in the registrational phase III studies. It is important to note that we have no information on the number of patients under treatment in the EV database. Conclusions: The EV database highlights several AEs that are not reported in registrational phase III studies as well as different AEs profiles according to age. Clinicians should consider these data when treating patients with castration-resistant prostate cancer with ABI or ENZ.