ENFORTUMAB vedotin induced cutaneous adverse events were independently associated with improved survival in patients with locally advanced or metastatic urothelial cancer, according to a large multi institutional cohort study.
Enfortumab vedotin is an antibody drug conjugate used to treat advanced urothelial cancer, with skin toxicity among its most common adverse effects. Although previous studies have suggested that these reactions may be associated with improved outcomes, it has remained unclear whether this relationship reflects the effects of enfortumab vedotin itself or concurrent immune checkpoint inhibitor therapy.
To investigate this question, researchers conducted a retrospective study of patients treated with enfortumab vedotin between 2020 and 2025. Patient characteristics were reviewed manually, and cutaneous adverse events were carefully attributed to enfortumab vedotin or alternative causes using a structured likelihood scoring system. Progression free survival and overall survival were analysed using multivariable Cox regression and landmark analyses to minimise immortal time bias.
The study included 449 patients with a mean age of 71.9 years, of whom 27.2% were female and 72.8% were male. Overall, 206 patients developed a cutaneous adverse event during treatment. Of these, 127 events were attributed to enfortumab vedotin, while 39 were classified as high grade.
The most frequently reported skin toxic effects were pruritus, affecting 41.3% of patients with cutaneous adverse events, followed by unspecified or desquamating dermatitis in 37.3% and morbilliform dermatitis in 27.7%.
Patients who developed enfortumab vedotin induced cutaneous adverse events experienced significantly improved outcomes. At the primary 30 day landmark analysis, these patients had longer progression free survival (hazard ratio:0.60; 95% CI:0.43–0.82; P<0.001) and overall survival (hazard ratio:0.46; 95% CI:0.31–0.67; P<0.001). The survival benefit remained consistent across all landmark analyses from 15–105 days.
Early onset enfortumab vedotin induced cutaneous adverse events were associated with improved survival throughout the study period. Importantly, high grade skin toxic effects were not associated with poorer survival outcomes.
The authors concluded that enfortumab vedotin induced cutaneous adverse events were independently associated with both improved progression free survival and overall survival, even after accounting for concurrent immune checkpoint inhibitor exposure and immortal time bias. They suggested that recognising the timing and morphology of these reactions may help inform both dermatological management and oncological decision making, while highlighting their potential value as a prognostic marker during treatment.
Reference
Lee E et al. Enfortumab Vedotin−Induced Cutaneous Toxic Effects and Survival in Urothelial Carcinoma. JAMA Dermatol. 2026;DOI:10.1001/jamadermatol.2026.2543
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