Ng Cheoklong, Jing Taile, Yu Shicheng, Ye Jianjun, Zhang Shun, Jia Zhankui, Tang Qi, Hu Xiaoyi, Chen Minfeng, Huang Weiping, Wu Jitao, Bi Hai, Yan Zejun, Shen Haibo, Xiong Wei, Liu Zheng, Xiao Jun, Zhang Tao, Wei Xuedong, Hu Hailong, Yang Qing, Yuan Yichu, Huang Zhiyang, Xue Wei, Bao Yige, Ding Guoqing, Xia Dan, Huang Jiwei
Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
The First Affiliated Hospital, School of Medcine, Zhejiang University, #79 Qingchun Rd., Hangzhou, 310003, Zhejiang Province, People's Republic of China.
Cancer Immunol Immunother. 2025 Sep 13;74(10):304. doi: 10.1007/s00262-025-04154-5.
Disitamab vedotin (DV, RC48-ADC) has shown promising efficacy and manageable safety as monotherapy or combined with immune checkpoint inhibitors (ICIs) in metastatic urothelial carcinoma (mUC) patients progressing after systemic chemotherapy. This study evaluates the efficacy and safety of RC48-ADC plus ICIs in metastatic upper tract urothelial carcinoma (mUTUC) in a real-world setting.
This retrospective, multicenter study included 198 mUTUC patients treated with RC48-ADC plus ICI at 23 clinical centers between June 2021 and December 2023. Data were analyzed from July to September 2024.
objective response rate (ORR). Secondary endpoints: progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to objective response, and treatment-related adverse events (TRAEs).
Among the patients, 122 (61.6%) received combination therapy as first-line treatment, while 76 (38.4%) as second-line or beyond. ORR was 58.6% (95% CI: 51.4-65.5), with a median PFS of 13.0 months; median OS was not reached. Subgroup analyses showed consistent ORR across all subgroups. Adverse events (AEs) occurred in 79.8% of patients, with grade 3-4 AEs in 19.7%. Common AEs included neuropathy (40.4%), fatigue (26.8%), alopecia (25.3%), and rash (21.7%). The main limitations of this study include its retrospective design and the population of the study only include patients from China, leading to potential selection bias.
RC48-ADC combined with ICIs demonstrated robust antitumor activity and a favorable safety profile in real-world mUTUC, particularly in selected patient groups. Further studies are needed to explore its potential in this high-risk population.
在接受全身化疗后进展的转移性尿路上皮癌（mUC）患者中，地西他滨维泊妥珠单抗（DV，RC48-ADC）作为单药治疗或与免疫检查点抑制剂（ICI）联合使用已显示出有前景的疗效和可管理的安全性。本研究评估了在真实世界中RC48-ADC联合ICI治疗转移性上尿路尿路上皮癌（mUTUC）的疗效和安全性。
这项回顾性多中心研究纳入了2021年6月至2023年12月期间在23个临床中心接受RC48-ADC联合ICI治疗的198例mUTUC患者。数据于2024年7月至9月进行分析。
客观缓解率（ORR）。次要终点：无进展生存期（PFS）、总生存期（OS）、缓解持续时间（DoR）、达到客观缓解的时间以及治疗相关不良事件（TRAEs）。
在这些患者中，122例（61.6%）接受联合治疗作为一线治疗，而76例（38.4%）作为二线或更后线治疗。ORR为58.6%（95%CI：51.4 - 65.5），中位PFS为13.0个月；中位OS未达到。亚组分析显示所有亚组的ORR一致。79.8%的患者发生不良事件（AE），3 - 4级AE发生率为19.7%。常见AE包括神经病变（40.4%）、疲劳（26.8%）、脱发（25.3%）和皮疹（21.7%）。本研究的主要局限性包括其回顾性设计，且研究人群仅包括来自中国的患者，导致潜在的选择偏倚。
RC48-ADC联合ICI在真实世界的mUTUC中显示出强大的抗肿瘤活性和良好的安全性，尤其是在特定患者群体中。需要进一步研究以探索其在这一高风险人群中的潜力。
