Retrospective cohort study of skin toxic effects and survival with enfortumab vedotin plus pembrolizumab in advanced urothelial carcinoma

Skin toxic effects are a common early adverse event of enfortumab vedotin plus pembrolizumab (EVP) therapy, but is association with clinical outcomes in patients receiving first-line therapy is uncertain. A retrospective cohort study at MD Anderson Cancer Center (Houston, TX) evaluated the association between treatment-emergent skin toxic effects and clinical outcomes among adults with locally advanced or metastatic urothelial carcinoma (aUC) receiving first-line EVP. In this cohort of 185 patients (median age 73 years; IQR 67-70; 75% male), skin toxic effects occurred in 98 (53%) at a median of 14 days (IQR 7-28) after EVP therapy initiation. Skin toxic effects of grade 3 or higher occurred in 10 patients (5.4%). At a median follow-up of 17.7 months (IQR 11.3-24.2), Simon-Makuch curves demonstrated longer overall survival (OS) and progression-free survival (PFS) among all patients and longer OS among patients with visceral metastases in the skin toxic effects stratum than in the no toxicity stratum. In adjusted time-dependent Cox proportional hazards regression, skin toxic effets were associated with longer OS (HR 0.34; 95% CI 0.20-0.57). In 30-day landmark analyses, associations with PFS and objective response rate remained directionally favorable but were attenuated after multivariable adjustment. The authors conclude that these findings support prospective validation of skin toxic effects as an early clinical marker of treatment benefit with first-line EVP for aUC.