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This study evaluates the efficacy and safety of RC48-ADC plus ICIs in metastatic upper tract urothelial carcinoma (mUTUC) in a real-world setting.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>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. Primary endpoint: 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).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Result<\/jats:title>\n            <jats:p>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\u201365.5), with a median PFS of 13.0\u00a0months; 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\u20134 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00262-025-04154-5","type":"journal-article","created":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T07:28:39Z","timestamp":1757748519000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The efficacy and safety of disitamab vedotin combined with immune checkpoint inhibitors in metastatic upper tract urothelial carcinoma: a multicenter real-world study"],"prefix":"10.1007","volume":"74","author":[{"given":"Cheoklong","family":"Ng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taile","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shicheng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhankui","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minfeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiping","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zejun","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuedong","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichu","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yige","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,13]]},"reference":[{"issue":"1","key":"4154_CR1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3322\/caac.21820","volume":"74","author":"RL Siegel","year":"2024","unstructured":"Siegel RL, Giaquinto AN, Jemal A (2024) Cancer statistics, 2024. 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