Risk Signals of Antibody-Drug Conjugates in Bladder Cancer: A Real-World FAERS Study.

Background: Antibody-drug conjugates (ADCs) represent a transformative class of therapeutics for advanced bladder cancer. However, their real-world safety profiles are not yet fully characterized. Methods: This retrospective pharmacovigilance study analyzed data from the FDA Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2024. Disproportionality analyses, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN), were used to detect significant adverse drug event (ADE) signals for four ADCs in bladder cancer treatment: enfortumab vedotin (EV), sacituzumab govitecan (SG), trastuzumab deruxtecan (DS-8201), and trastuzumab emtansine (T-DM1). Results: Among 494 analyzed reports, EV constituted the majority (91.7%). Distinct safety signals were identified for each ADC: EV was strongly associated with skin disorders and metabolic disturbances; SG was primarily linked to gastrointestinal events, with emerging signals of renal abnormalities; DS-8201 was associated with systemic administration-related issues; and T-DM1 showed signals for respiratory and bleeding events. Notably, oral candidiasis related to EV was not explicitly highlighted in the current prescribing information. Conclusion: This study delineates the safety profiles of ADC therapies for bladder cancer, confirming known risks and identifying potential new signals. The findings highlight the need for ADC-specific monitoring strategies and proactive management protocols to mitigate toxicities, thereby providing essential evidence for clinical decision-making.