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Título

ENFORTUMAB VEDOTIN-RELATED CUTANEOUS TOXICITIES IN PATIENTS WITH UROTHELIAL CARCINOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS

Resumo

Introduction: Enfortumab vedotin (EV) is an antibody-drug conjugate, targeting nectin-4, that delivers microtubule-disrupting agent monomethyl auristatin E (MMAE) to cancer cells. Cutaneous toxicities are associated with nectin-4 expression in the skin and have been reported in several clinical trials. Hence, we conducted a systematic review and meta-analysis to investigate EV-related cutaneous adverse events.

Methods: We systematically searched Pubmed, Cochrane, and Embase for clinical trials (CTs) reporting the incidence of EV-related cutaneous toxicities in patients with locally advanced or metastatic urothelial carcinoma. Observational studies and abstracts were excluded. We pooled all-grade, grade 3 or higher, and severe cutaneous treatment-related adverse events (TRAE) and presented them as overall incidence rates and 95% confidence intervals (95% CI). Statistical analyses were performed using R software, and heterogeneity was evaluated through I2 statistics.

Results: Of 1,047 reports, five CTs involving 751 participants met the inclusion criteria. Median age ranged from 64 to 75 years, and 75% (567) were male. Most patients had prior platinum-based chemotherapy. The median follow-up of each study and median time to onset of skin toxicity varies from 10.2 to 16.4 and 0.42-0.95 months, respectively. In a pooled analysis of all studies, any grade skin reactions were present in 48.51% (95% CI 43.64-53.39, I2 44%) of patients, and grade ≥ 3 in 11.41% (7.97-16.10, I2 59%). The most frequent cutaneous TRAE was rash maculopapular, with an overall frequency of 40.25% (95% CI 30.21-50.29, I2 89%), and 5.31% (3.34-8.34, I2 40%) rate of grade ≥ 3. Alopecia was seen in 40.52% (95% CI 41.87-49.17, I2 11%) of patients, pruritus in 28.58% (22.21-35.94, I2 68%), and dry skin in 21.13% (17.06-25.87, I2 0%). Notably, the severe cutaneous toxicity incidence was 19.26% (15.90-23.13, I2 0%). Six cases of bullous dermatitis, five of palmar-plantar erythrodysesthesia, and one case of Stevens-Johnson syndrome were reported. Most cutaneous toxicities were mild to moderate in severity and manageable with dose reduction, interruption, and supportive treatment.

Conclusions: Despite the higher incidence of EV-related cutaneous toxicities, most cases were manageable with supportive care, dose reduction, and drug interruption. EV is an excellent drug for urothelial carcinoma patients; therefore, understanding EV-related skin toxicities is paramount for comprehensive patient care.