Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: The occurrence of EV-related peripheral neuropathy might be associated with the efficacy of EV therapy in mUC patients.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: The occurrence of EV-related peripheral neuropathy might be associated with the efficacy of EV therapy in mUC patients.
摘要：
背景：Enfortumabvedotin（EV）被批准用于2021年9月在日本接受抗癌治疗后进展的转移性尿路上皮癌（mUC）患者。EV相关副作用的发生与临床结果之间的关联仍有待阐明。
方法：我们确定了从批准之日起至2023年3月在我们的五个机构接受EV治疗的97例mUC患者。中位随访期为7.0个月。回顾性分析EV的疗效和安全性。
结果：患者的中位年龄为71岁，39%的PS为1或更高，原发性上尿路肿瘤占56.7%。对EV治疗的总体反应率（ORR），中位无进展生存期（PFS），总生存率(OS)为43.3%,7.52个月，12.78个月，分别。任何级别的治疗相关皮肤病，熟食症,周围神经病变,胃肠道疾病,和高血糖发生在61（62.9%），36（37.1%），34（35.1%），29（29.9%），和18名(18.6%)患者，分别。EV相关周围神经病变患者的ORR明显较高(58.8%vs.34.9%,P=.032）和更长的PFS中位数（8.05vs.6.31个月，P=.017)和OS(未达到与11.57个月，P=.008，分别）比没有的。EV治疗后周围神经病变的发生和腹膜播散的存在是与PFS（风险比分别为0.46，P=.008和风险比分别为3.83，P=.004）和OS（风险比分别为0.30，P=.005和风险比分别为4.53，P=.002）独立相关的因素。
结论：在mUC患者中，EV相关周围神经病变的发生可能与EV治疗的疗效有关。
方法：我们确定了从批准之日起至2023年3月在我们的五个机构接受EV治疗的97例mUC患者。中位随访期为7.0个月。回顾性分析EV的疗效和安全性。
结果：患者的中位年龄为71岁，39%的PS为1或更高，原发性上尿路肿瘤占56.7%。对EV治疗的总体反应率（ORR），中位无进展生存期（PFS），总生存率(OS)为43.3%,7.52个月，12.78个月，分别。任何级别的治疗相关皮肤病，熟食症,周围神经病变,胃肠道疾病,和高血糖发生在61（62.9%），36（37.1%），34（35.1%），29（29.9%），和18名(18.6%)患者，分别。EV相关周围神经病变患者的ORR明显较高(58.8%vs.34.9%,P=.032）和更长的PFS中位数（8.05vs.6.31个月，P=.017)和OS(未达到与11.57个月，P=.008，分别）比没有的。EV治疗后周围神经病变的发生和腹膜播散的存在是与PFS（风险比分别为0.46，P=.008和风险比分别为3.83，P=.004）和OS（风险比分别为0.30，P=.005和风险比分别为4.53，P=.002）独立相关的因素。
结论：在mUC患者中，EV相关周围神经病变的发生可能与EV治疗的疗效有关。
