Adverse Events Associated with Lutetium-177-PSMA-617 (Pluvicto®) in Advanced Prostate Cancer: Insights from the FDA's Adverse Event Reporting System (FAERS)

Objective Pluvicto® (Lutetium-177–PSMA-617) was the world's first radiolabeled drug for the treatment of metastatic castration-resistant prostate cancer that was positive for prostate-specific membrane antigen with limited global use to date. Our study aimed to conduct a thorough analysis based on the adverse event reporting system FAERS of the Food and Drug Administration (FDA), providing insights for its future clinical application. Methods The adverse event reports suspected primarily of Pluvicto® from April 1, 2022 to December 31, 2024 were retrieved from the FAERS system to conduct a disproportionality test. The characteristics of these reports were analyzed including demographic features, time of adverse event occurrence, and features of adverse events. Adverse events (AEs) were classified by System Organ Classes (SOCs) and preferred terms (PTs) according to the Medical Dictionary for Regulatory Activities (MedDRA®). The disproportionality of results was analyzed by Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Results A total of 7654 adverse event reports suspected primarily of Pluvicto® were submitted to the database, showing a monthly increasing trend in report numbers. 649 Preferred Terms (PTs) were identified, and after screening, from which 33 significant PT signals were identified by the 4 algorithms, involving 10 SOCs after classification. Additionally, our study revealed thrombotic microangiopathy (TMA) as an adverse event not previously documented in the label. Conclusions The study confirmed the majority of significant AE signals that have been listed in the prescribing information or reported in previous studies. It was recommended that intensified laboratory monitoring and screening of clinical parameters, baseline hepatic function and potential infestation risks during initial treatment phases.