Enfortumab Vedotin–Related Skin Toxicities Predict Better Survival in Advanced Urothelial Cancer: JAMA
USA: Researchers have found in a recent cohort study that cutaneous adverse events (cAEs) associated with enfortumab vedotin (EV) were independently linked to improved progression-free survival (PFS) and overall survival (OS) in patients with locally advanced or metastatic urothelial cancer. These findings suggest that EV-induced skin toxicities may serve as a valuable prognostic marker, emphasizing the importance of accurately distinguishing them from other skin conditions to optimize both oncologic and dermatologic management.
The findings were published in JAMA Dermatology by Eudora Lee, BS, Harvard Medical School, Boston, Massachusetts, and colleagues.
Enfortumab vedotin is an antibody-drug conjugate approved for the treatment of locally advanced or metastatic urothelial cancer. Skin-related adverse events are common during EV therapy, but it has remained uncertain whether these reactions independently predict improved outcomes or are influenced by concurrent immune checkpoint inhibitor (ICI) treatment. To clarify this, researchers evaluated the relationship between EV-induced cutaneous adverse events and survival, as well as the timing and clinical characteristics of these skin reactions.
The multi-institutional retrospective cohort study evaluated 449 patients with locally advanced or metastatic urothelial cancer treated with enfortumab vedotin (EV) between 2020 and 2025. Researchers used manual chart review and a likelihood scoring system to attribute cutaneous adverse events to EV or other causes. They assessed progression-free and overall survival using Kaplan-Meier and multivariable Cox regression analyses. The mean participant age was 71.9 years; 27.2% were women and 72.8% were men.
Key findings from the study include:
- 206 patients (45.9%) developed cutaneous adverse events during EV treatment, with 127 cases (61.7%) attributed directly to enfortumab vedotin.
- The most frequently observed EV-related skin toxicities were pruritus, unspecified or desquamating dermatitis, and morbilliform dermatitis.
- Patients who developed EV-induced cutaneous adverse events experienced significantly longer progression-free survival and overall survival than those without these reactions.
- At the primary 30-day landmark analysis, EV-induced skin toxicities were associated with a 40% lower risk of disease progression (HR, 0.60) and a 54% lower risk of death (HR, 0.46).
- Early-onset EV-induced cutaneous adverse events remained associated with improved survival across all landmark analyses, while high-grade skin toxicities were not linked to poorer survival outcomes.
The researchers concluded that EV-induced cutaneous adverse events were independently associated with improved progression-free and overall survival, even after adjusting for immortal time bias and immune checkpoint inhibitor exposure. They noted that accurately identifying these skin toxicities may help optimize oncologic and dermatologic management while serving as a potential prognostic marker during EV treatment.
Reference:
Lee E, Karagenova R, Lu C, et al. Enfortumab Vedotin−Induced Cutaneous Toxic Effects and Survival in Urothelial Carcinoma. JAMA Dermatol. Published online July 29, 2026. doi:10.1001/jamadermatol.2026.2543
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