Real-world analysis of the efficacy and safety of enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma: A multicenter retrospective study.

712 Background: We investigated the efficacy and safety enfortumab vedotin (EV) in patients with locally advanced or metastatic urothelial carcinoma in real-world practice. Methods: This multicenter retrospective study included 419 patients treated for locally advanced or metastatic urothelial carcinoma between April 2004 to April 2024. The patients were categorized into the following three groups: 87 patients who underwent first-line chemotherapy and sequential chemotherapy alone (chemo-alone group), 217 patients who underwent maintenance immunotherapy or second-line immunotherapy after first-line chemotherapy (chemo-ICI group) and 115 patients who were treated with EV after first-line chemotherapy and immunotherapy (chemo-ICI-EV group). The primary outcome was the comparison of progression-free survival (PFS) of first-line therapy and overall survival (OS) from first-line therapy between the three treatment groups. Secondary outcomes included the efficacy and safety in the chemo-ICI-EV group focusing on skin adverse events (AEs). Results: The OS from first-line therapy was significantly longer in the chemo-ICI-EV group than that in the other groups. There was no significant difference in the first-line PFS of first-line therapy between the three groups. A multivariable Cox regression analysis showed the administration of EV was significantly associated with prolonged OS. Skin AEs were observed in 69 (60%) as a major adverse event. The PFS and OS in the patients with skin AEs was significantly longer than in the patients without skin AEs despite the reduced dose of EV. A multivariable Cox regression analysis showed that skin AEs were significantly associated with prolonged RFS and OS. Conclusions: The administration of EV significantly improved oncological outcomes in the real-world practice. Dose adjustment of EV may be key for long-term use and oncological outcomes.