Comparative safety analysis of enfortumab vedotin and pembrolizumab: monotherapy vs. combination therapy insights from FDA adverse event reporting system data.

[OBJECTIVE] To analyze adverse events (AEs) associated with enfortumab vedotin (EV) and pembrolizumab (PB) monotherapy and combination therapy using the FDA Adverse Event Reporting System database (FAERS).

[METHODS] A retrospective pharmacovigilance study was conducted using FAERS data. Data were classified into EV monotherapy, PB monotherapy, and combination therapy groups. Disproportionality analysis was conducted to identify the overall distribution and specific AEs. The results were compared with drug labels for cross-validation. High-evidence positive signal AEs were obtained by matching the signals from the MHRA integrated method and the MGPS method, and differences between monotherapy and the combination therapy were compared.

[RESULTS] The results compared with the package inserts showed that the results well reflected the AEs reported in the package inserts. In addition, 40 new AEs with dual positive signals were identified in the combination therapy, which were not reported or had significantly lower signal intensity in monotherapy, including various infections and inflammations, blood pressure fluctuations, taste loss, and neurological issues. There were 27 AEs with dual positive signals in EV and PB monotherapy, but the signal intensity of these AEs was significantly reduced in combination therapy, like adrenal cortical insufficiency, bone marrow suppression, skin and subcutaneous tissue diseases, and gastrointestinal ulcers and perforations.

[CONCLUSIONS] The overall safety of the combination therapy may be superior to that of monotherapy, suggesting that the synergistic effect of combination may also operate in the safety dimension. Some newly identified AEs with positive signals reported only in combination therapy required attention and verification through further studies.