Enfortumab vedotin-related skin toxicities in patients with urothelial carcinoma: A systematic review and meta-analysis

Background: Enfortumab vedotin (EV) is an antibody-drug conjugate that binds nectin-4, a cell-adhesion molecule highly expressed in urothelial carcinoma (UC) and epidermal keratinocytes. Dermatologic events have become important EV-related toxicities in clinical trials and observational studies. We conducted a systematic review and meta-analysis on dermatological toxicity in UC patients treated with EV. Methods: We systematically searched PubMed, Cochrane, and Embase for clinical trials (CT) and observational studies reporting EV-related cutaneous toxicities in UC patients. We investigated all-grade and grade ≥ 3 treatment-related adverse events (TRAE) and severe cutaneous adverse reactions (SCAR) in UC patients. The outcomes were presented as overall incidence rates and 95% confidence intervals (95% CI). Statistical analyses were performed using R software. Results: 30 studies comprising 2,554 participants were included, of which 72% (n = 1,845) were male. In a pooled analysis, all-grade skin reaction rate was 49% (95% CI 42%–56%), and grade ≥ 3 events were observed in 10% (95% CI 8%–13%) of cases. The incidence of all-grade and grade ≥ 3 SCAR was 19% (95% CI 16%–23%) and 5% (95% CI 3%–7%), respectively. The frequency of alopecia, pruritus, and dry skin were as follows: 29%, 26%, and 22%. The incidence of all-grade rash was 27%, with maculopapular rash (19%), and erythematous rash (6%) as the most common types. Conclusions: To our knowledge, this is the first meta-analysis to characterize EV-related dermatological toxicities. While most cases are manageable, patients on EV should be closely monitored for cutaneous AEs to prevent serious complications and to maintain treatment efficacy.