The real-world safety profile of enfortumab vedotin with or without pembrolizumab: insights from a comparative analysis of FAERS.

Authors

Heng Chen, Juanjuan Huang, Gefei He

Published in

Frontiers in immunology. Volume 17. Pages 1831172. Epub Jul 24, 2026.

Abstract

The combination of enfortumab vedotin and pembrolizumab (EV+P) has revolutionized advanced urothelial carcinoma treatment, yet their combined real-world safety profile remains insufficiently characterized. This study aimed to quantitatively compare the adverse event (AE) landscapes of EV+P and EV monotherapy using the FAERS data.
A case/non-case study design was conducted on FAERS data from 2020 Q4 to 2025 Q3. Disproportionality signals were evaluated at the System Organ Class (SOC), High-Level Group Term (HLGT), and Preferred Term (PT) levels. Time-to-onset was analyzed using the Kaplan-Meier method, and narrative review was performed to validate pneumonitis signals.
We identified 3, 004 and 2, 265 AE reports for EV and EV+P, respectively. EV+P demonstrated significantly higher risks across nine SOCs, most notably in endocrine (OR: 5.88), immune system (OR: 2.03), and respiratory (OR: 1.71) disorders. At the PT level, EV+P was strongly associated with hepatitis (OR: 14.79), immune-mediated enterocolitis (OR: 11.77), adrenal insufficiency (OR: 9.14), and pneumonitis (OR: 2.75). Potential novel signals like hearing disorders (OR: 10.64) and dental/gingival conditions (OR: 9.31) were noted but lacked statistical robustness post-correction. Literature validation confirmed a higher incidence of any-grade pneumonitis with EV+P (10% vs. 3.5%). Furthermore, EV+P suggested a potentially earlier onset for several toxicities, including eye (FDR P = 0.047) and skin disorders (FDR P = 0.011).
EV + P demonstrates a broader and more intense AE spectrum than EV monotherapy, driven largely by immune-related toxicities and potential synergistic organ injury. These findings emphasize the need for vigilant clinical monitoring and early intervention when employing this combination therapy.

PMID:
42568649
Bibliographic data and abstract were imported from PubMed on 08 Aug 2026.

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