[EFFICACY AND SAFETY OF ENFORTUMAB VEDOTIN IN ADVANCED UROTHELIAL CARCINOMA TREATMENT: AN INITIAL EXPERIENCE IN A SINGLE INSTITUTION].

(Purpose) Enfortumab vedotin has been available as a third-line treatment for advanced urothelial carcinoma in Japan since December 2021. While the treatment is expected to improve the outcome of advanced urothelial carcinoma, concerns regarding adverse events do exist. We report here our initial experience of the use of enfortumab vedotin as a third-line therapy in patients with advanced urothelial carcinoma. (Patients and Methods) We retrospectively evaluated the efficacy and adverse events of enfortumab vedotin treatment, as a third line therapy, in patients who had failed platinum-containing chemotherapy and immune checkpoint inhibitor therapy in our institution from January 2022 to January 2023. Efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and duration of response (DOR). Safety was evaluated for treatment-related adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) ver. 4.0. (Results) In this study, sixteen patients were investigated. The median age was 70 years (45-93 years); all patients had previously received platinum-containing chemotherapy with cisplatin or carboplatin, eleven having been treated with pembrolizumab, and 5 with avelumab, as sequential immune checkpoint inhibitors. As for efficacy, the median observation period was 9.27 months (4.03-16.6 months). The treatment response rate included 2 complete response (CR) (12.5%), 5 partial response (PR) (31.3%), and 5 stable disease (SD), out of 16 patients. The ORR and DCR were 43.8% and 75.0%, respectively. The median PFS was 7.77 months (3.67-not reached). The median time to response was 1.87 months (0.47-2.80 months) and the median DOR was 7.93 months (0.73-13.1 months). Eight patients (50%) discontinued treatment due to disease progression. As for safety, the incidence of treatment-related adverse events (TRAE) was 93.8%, and that of Grade 3 or higher TRAE was 56.3%. Four out of 16 patients (25%) underwent dose reduction due to TRAE. Among all grades, skin reactions were the most common in 12 patients (75%), followed by dysgeusia, alopecia, neutropenia, and anorexia. Neutropenia (including febrile neutropenia) was the most common Grade 3 or higher TRAE in five patients (31.3%), followed by skin reactions, anorexia, and anemia. Two of the patients, who observed skin reactions, developed severe rash and Stevens-Johnson syndrome, which eventually led to treatment discontinuation. The median time from enfortumab vedotin administration to onset of skin reaction was 9 days (5-18 days), with most cases occurring in the first cycle. (Conclusions) Enfortumab vedotin is an effective treatment option in real clinical practice. However, adverse events, including skin reactions, should be carefully monitored.