Association between response to enfortumab vedotin and peripheral neuropathy in urothelial carcinoma patients: a multicenter retrospective study

• Published in: Japanese journal of clinical oncology 2024-11, Vol.54 (11), p.1194-1200
• Main Authors: Hayakawa, Nozomi, Kikuchi, Eiji, Kaneko, Go, Yamashita, Ryo, Ikarashi, Daiki, Endo, Yuki, Usui, Kimitsugu, Obara, Wataru, Oyama, Masafumi, Kondo, Yukihiro
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Carcinoma, Transitional Cell - drug therapy; Carcinoma, Transitional Cell - pathology; Female; Humans; Male; Middle Aged; Peripheral Nervous System Diseases - chemically induced; Progression-Free Survival; Retrospective Studies; Urologic Neoplasms - drug therapy; Urologic Neoplasms - pathology
• ISSN: 1465-3621; 1465-3621
• DOI: 10.1093/jjco/hyae082

Enfortumab vedotin (EV) was approved for patients with metastatic urothelial carcinoma (mUC) who progressed after anticancer therapy on September 2021 in Japan. The association between the occurrence of EV-related side effects and clinical outcome remains to be elucidated. We identified 97 mUC patients treated with EV therapy at our five institutions from the date of approval to March 2023. The median follow-up period was 7.0 months. We retrospectively analyzed the efficacy and safety of EV. The median age of the patients was 71 years old, 39% had PS of 1 or more, and 56.7% had primary tumor in upper urinary tract. Overall response rate (ORR) to EV therapy, median progression-free survival (PFS), and overall survival (OS) were 43.3%, 7.52 months, and 12.78 months, respectively. Any grade of treatment-related skin disorder, dysgeusia, peripheral neuropathy, gastrointestinal disorder, and hyperglycemia occurred in 61 (62.9%), 36 (37.1%), 34 (35.1%), 29 (29.9%), and 18 (18.6%) patients, respectively. The patients with EV-associated peripheral neuropathy had significantly higher ORR (58.8% vs. 34.9%, P = .032) and longer median PFS (8.05 vs. 6.31 months, P = .017) and OS (not reached vs. 11.57 months, P = .008, respectively) than those without. The occurrence of peripheral neuropathy after EV treatment and the presence of peritoneal dissemination were factors independently associated with PFS (hazard ratio = 0.46, P = .008 and hazard raito = 3.83, P = .004, respectively) and OS (hazard ratio = 0.30, P = .005 and hazard raito = 4.53, P = .002, respectively). The occurrence of EV-related peripheral neuropathy might be associated with the efficacy of EV therapy in mUC patients.