The efficacy and safety of disitamab vedotin combined with immune checkpoint inhibitors in metastatic upper tract urothelial carcinoma: a multicenter real-world study

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.