Physical, but not laboratory, treatment-related adverse events are associated with favorable outcomes of enfortumab vedotin for advanced urothelial carcinoma: A landmark analysis.
Satoru Taguchi: Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. ORCID
Taketo Kawai: Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. ORCID
Yoshiki Ambe: Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Kenjiro Kishitani: Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Michio Noda: Department of Urology, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan.
Tomoyuki Kaneko: Department of Urology, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan. ORCID
Jimpei Miyakawa: Department of Urology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Yu Nakamura: Department of Urology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Hayato Hoshina: Department of Urology, Jichi Medical University, Shimotsuke, Tochigi, Japan. ORCID
Daisuke Obinata: Department of Urology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan. ORCID
Kenya Yamaguchi: Department of Urology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan. ORCID
Shigenori Kakutani: Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Yoshitsune Furuya: Department of Urology, The Fraternity Memorial Hospital, Sumida-ku, Tokyo, Japan.
Yujiro Sato: Department of Urology, The Fraternity Memorial Hospital, Sumida-ku, Tokyo, Japan.
Yume Adachi: Department of Urology, Musashino Red Cross Hospital, Musashino, Tokyo, Japan.
Kazuma Sugimoto: Department of Urology, Center Hospital of the National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan.
Keigo Sato: Department of Urology, Center Hospital of the National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan.
Mariko Tabata: Department of Urology, The Institute of Medical Science, The University of Tokyo, Minato-Ku, Tokyo, Japan.
Takehiro Tanaka: Department of Pharmacy, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan.
Katsuhiko Nara: Department of Pharmacy, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan.
Yukari Uemura: Biostatistics Section, Department of Data Science, Center of Clinical Sciences, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan.
Jun Kamei: Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Yoshiyuki Akiyama: Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Yusuke Sato: Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Yuta Yamada: Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. ORCID
Aya Niimi: Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. ORCID
Daisuke Yamada: Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Tappei Takada: Department of Pharmacy, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan.
Sayuri Takahashi: Department of Urology, The Institute of Medical Science, The University of Tokyo, Minato-Ku, Tokyo, Japan.
Yukio Yamada: Department of Urology, Musashino Red Cross Hospital, Musashino, Tokyo, Japan.
Hideyo Miyazaki: Department of Urology, Center Hospital of the National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan.
Yutaka Enomoto: Division of Urology, Mitsui Memorial Hospital, Chiyoda-ku, Tokyo, Japan.
Hiroaki Nishimatsu: Department of Urology, The Fraternity Memorial Hospital, Sumida-ku, Tokyo, Japan.
Tetsuya Fujimura: Department of Urology, Jichi Medical University, Shimotsuke, Tochigi, Japan. ORCID
Hiroshi Fukuhara: Department of Urology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Tohru Nakagawa: Department of Urology, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan.
Satoru Takahashi: Department of Urology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan. ORCID
Haruki Kume: Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
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 patientdied 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.
