Kosuke Iwatani, Fumihiko Urabe, Keiichiro Mori, Juria Nakano, Kensuke Fujiwara, Shun Saito, Shuhei Hara, Shota Kawano, Mimu Ishikawa, Wataru Fukuokaya, Yu Imai, Sotaro Kayano, Kanako Kasai, Takafumi Yanagisawa, Kojiro Tashiro, Masaya Murakami, Shunsuke Tsuzuki, Yuma Waki, Jun Miki, Takahiro Kimura
INTRODUCTION: Enfortumab vedotin plus pembrolizumab (EVP) has shown promising efficacy in locally advanced or metastatic urothelial carcinoma (la/mUC), but real-world data in Japanese patients are limited. We assessed the safety and early efficacy of EVP, with a focus on cutaneous adverse events (AEs). METHODS: We retrospectively analyzed 48 Japanese patients with la/mUC treated with first-line EVP at 12 centers between November 2024 and March 2025. Clinical data, AEs, and tumor responses were collected. Cutaneous AEs were evaluated for onset, severity, and management. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RESULTS: The patients' median age was 76 years, and 89.6% were cisplatin-ineligible. All patients experienced treatment-related AEs, with 39.6% having grade ≥3 events. Cutaneous AEs occurred in 60.4%, including 18.8% with grade ≥3 rash and two cases of Stevens-Johnson syndrome. The median time to discontinuation due to AEs was 14 days. The overall response rate was 39.6%, and the disease control rate was 69%, rising to 87% among 38 evaluable patients. CONCLUSION: EVP demonstrated favorable early efficacy in Japanese patients but was associated with frequent early discontinuation due to AEs, particularly cutaneous toxicity. Early skin care and interdisciplinary management are essential. These findings support EVP use while emphasizing AE management and patient-centered care.