Satoru Taguchi, Taketo Kawai, Yoshiki Ambe, Kenjiro Kishitani, Michio Noda, Tomoyuki Kaneko, Jimpei Miyakawa, Yu Nakamura, Hayato Hoshina, Daisuke Obinata, Kenya Yamaguchi, Shigenori Kakutani, Yoshitsune Furuya, Yujiro Sato, Yume Adachi, Kazuma Sugimoto, Keigo Sato, Mariko Tabata, Takehiro Tanaka, Katsuhiko Nara, Yukari Uemura, Jun Kamei, Yoshiyuki Akiyama, Yusuke Sato, Yuta Yamada, Aya Niimi, Daisuke Yamada, Tappei Takada, Sayuri Takahashi, Yukio Yamada, Hideyo Miyazaki, Yutaka Enomoto, Hiroaki Nishimatsu, Tetsuya Fujimura, Hiroshi Fukuhara, Tohru Nakagawa, Satoru Takahashi, Haruki Kume
International journal of urology : official journal of the Japanese Urological Association 32(3) 270-276 2025年3月
BACKGROUND: While the occurrence of immune-related adverse events has been recognized as a prognostic marker in patients receiving immune checkpoint inhibitors, the prognostic significance of treatment-related adverse events (trAEs) in patients undergoing antibody-drug conjugates such as enfortumab vedotin (EV) is controversial. METHODS: We reviewed 106 patients with advanced urothelial carcinoma who were treated with EV therapy at 10 institutions between 2021 and 2023. Associations of clinical parameters with overall survival and progression-free survival were assessed using the Cox proportional hazards model. For the assessment of trAEs, landmark analysis was conducted to minimize immortal time bias. RESULTS: Of 106 patients, 55 (51.9%) experienced disease progression and 44 (41.5%) died during the follow-up period. Any grade and grade ≥3 trAEs occurred in 94 (88.7%) and 44 (41.5%) patients, respectively. Common trAEs included skin disorders (74.5%), gastrointestinal disorders (62.3%), fatigue (50.0%), peripheral neuropathy (36.8%), and hematological disorders (37.7%). One patient died of interstitial pneumonia (grade 5). According to landmark analysis using 88 patients who survived for 2 months or more, trAEs were significantly associated with longer survival. Furthermore, when trAEs were classified into "physical trAEs" such as skin disorders and "laboratory trAEs" such as hematological disorders, the former were associated with longer survival while the latter were associated with shorter survival. CONCLUSIONS: Physical, but not laboratory, trAEs are associated with favorable outcomes of EV therapy for advanced urothelial carcinoma. Both managing trAEs and utilizing them as prognostic markers are key points in the use of antibody-drug conjugates such as EV.