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

Abstract

761 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 (CT) and observational studies. We conducted a systematic review and meta-analysis on skin toxicity in UC patients treated with EV. Methods: We systematically searched Pubmed, Cochrane, and Embase for published CT and observational studies reporting EV-related skin toxicities in UC patients. We investigated treatment-related adverse events (TRAE) and severe cutaneous adverse reactions (SCAR) in UC patients of all-grade and ≥ 3. The outcomes were presented as overall incidence rates and 95% confidence intervals (95% CI). Statistical analyses were performed using R software. Results: Ten studies comprising 1,061 participants were included. Median age ranged from 66 to 76 years, and 74% (783) were male. 72% of patients had prior immune checkpoint inhibitors. The median time to onset of skin toxicity varied from two to four weeks. In a pooled analysis, the skin reaction rate for all-grade of UC was 50% (95% CI 38-61), while for grade ≥ 3 was 10% (95% CI 7-15). The incidence of SCAR was 19% (95% CI 16-23) and 8% (95% CI 3-18) for grade ≥ 3. Alopecia was seen in 37% of patients, pruritus in 22% and dry skin in 21%. All-grade rash incidence rate was 29% and the most reported was maculopapular rash 22%, followed by erythematous rash (6%). Important cutaneous reactions included bullous dermatitis in 2.91% of patients (95% CI 1-6), palmar-plantar erythrodysesthesia in 2.46% (95% CI 1-5), Stevens-Johnson syndrome in 1.46% (95% CI 0.4-5), and toxic epidermal necrolysis in 0.95% (95% CI 0.2-4) of patients. Conclusions: This is the first study to characterize EV-related dermatological toxicities. We found a high incidence of all-grade events and a moderate frequency of severe and grade ≥ 3 toxicities. This study intends to highlight the need for close monitoring and adequate treatment for skin toxicities in UC patients receiving EV.