Real-world safety of first-line enfortumab vedotin plus pembrolizumab in advanced urothelial carcinoma: evidence from VigiBase and FAERS

BackgroundCompared with platinum-based chemotherapy, the combination of enfortumab vedotin and pembrolizumab (EV + Pembro) achieves higher durable response rates and improves survival outcomes in patients with locally advanced or metastatic urothelial carcinoma. As the first regimen pairing an immune checkpoint inhibitor with an antibody-drug conjugate, it offers a novel, effective option.

Yet evidence has largely been derived from clinical trials, and robust, comprehensive real-world characterization of adverse drug events (ADEs) remains limited. It is therefore essential to examine recent real-world data to delineate the safety profile of EV + Pembro with greater precision.MethodsWe conducted disproportionality analyses of ADE reports related to EV + Pembro from the FDA Adverse Event Reporting System (FAERS) and the WHO VigiBase.

Signal detection algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Multi-item Gamma Poisson Shrinker (MGPS), and Bayesian Confidence Propagation Neural Network (BCPNN), were used to identify significant safety signals. Additionally, the time to onset of ADEs was assessed.ResultsA total of 892 reports from VigiBase and 1,698 reports from FAERS were analyzed across 25 system organ classes.