EV-Related Skin Toxic Effects Associated With Improved Survival in Urothelial Cancer: Analysis
Key Takeaways
- About half of patients treated with enfortumab vedotin (EV) developed cutaneous adverse events (cAEs), most of which were attributed to EV and were low grade, a new analysis suggests.
- EV-induced cAEs were independently associated with significantly longer progression-free and overall survival, even after accounting for immune checkpoint inhibitor exposure and immortal time bias.
- Early recognition of EV-related skin toxic effects may offer prognostic insight while helping guide multidisciplinary management.
Cutaneous adverse events (cAEs) that develop during treatment with enfortumab vedotin (EV) may serve as a favorable prognostic marker in patients with locally advanced or metastatic urothelial carcinoma, according to a new study published online in JAMA Dermatology.
EV-Related Skin Toxic Effects May Signal Better Outcomes
Investigators evaluated 449 patients treated with EV between 2020 and 2025 to determine whether EV-induced cAEs were associated with survival independent of immune checkpoint inhibitor (ICI)-related skin toxicities. Among the cohort, 206 patients (45.9%) developed a cAE, with 127 events (61.7%) attributed to EV. High-grade reactions occurred in 39 patients (18.9%).
The most frequently reported EV-associated skin toxic effects were pruritus (41.3%), unspecified or desquamating dermatitis (37.3%), and morbilliform dermatitis (27.7%). Across all treatment groups, patients who developed EV-induced cAEs experienced significantly longer progression-free survival (PFS) and overall survival (OS). In the primary 30-day landmark analysis, EV-induced cAEs were associated with a 40% reduction in the risk of disease progression (hazard ratio [HR], 0.60; 95% CI, 0.43-0.82; P < 0.001) and a 54% reduction in the risk of death (HR, 0.46; 95% CI, 0.31-0.67; P < 0.001). Similar findings were observed across landmark analyses ranging from 15 to 105 days.
Early-onset EV-induced cAEs remained associated with improved outcomes, while high-grade skin toxic effects were not linked to worse survival.
"In this cohort study, EV-induced cAEs were independently associated with improved PFS and OS in patients with locally advanced or metastatic urothelial cancer, even after accounting for immortal time bias and ICI exposure," the authors wrote. "Distinguishing EV-induced cAEs from other causes in timeline and morphologic mechanisms may help guide oncologic and dermatologic treatment and management."
Source
Lee E, Karagenova R, Lu C, et al. JAMA Dermatol. Published online July 29, 2026. Doi:10.1001/jamadermatol.2026.2543