Disitamab vedotin (RC48) combined with PD-1 inhibitors in locally advanced or metastatic urothelial carcinoma: clinical outcomes and prognostic factors from a multicenter real-world study.

Background and objectives: The combination of disitamab vedotin (RC48) with PD-1 inhibitors has shown synergistic potential in preclinical studies for treating advanced urothelial carcinoma (UC). Nevertheless, real-world evidence regarding its clinical efficacy and safety profile remains limited. This multicenter real-world study aims to comprehensively evaluate the therapeutic outcomes and safety of RC48 combined with PD-1 inhibitors in patients with locally advanced or metastatic urothelial carcinoma (La/mUC), with a particular focus on analyzing the impact of comorbidities on treatment efficacy and prognosis. Patients and methods: A retrospective analysis was conducted on 132 patients with La/mUC who received RC48 combined with a PD-1 inhibitor at six treatment centers between June 2022 and March 2024. Clinical-pathological characteristics, treatment regimens, and follow-up data were collected from electronic medical record systems. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Safety was assessed by recording treatment-related adverse events (TRAEs), with efficacy evaluated across different disease subpopulations. Survival curves were generated using the Kaplan-Meier method, and Cox proportional hazards regression was employed for survival analysis. Results: A total of 132 patients with La/mUC were enrolled. The RC48 plus PD-1 inhibitor regimen demonstrated an ORR of 71.21% (95% CI: 62.97%-78.25%) and a DCR of 88.64% (95% CI: 82.10%-92.99%). The median PFS was 21 months (95% CI: 14-24 months), and the median OS was not reached. Kaplan-Meier analyses indicated that comorbid conditions such as hypertension, diabetes, hyperlipidemia, or renal insufficiency did not compromise efficacy, with similar PFS and OS observed across subgroups. The most common TRAEs were fatigue (38.64%), nausea (35.61%), anemia (32.58%), pruritus (28.79%), and peripheral neuropathy (23.48%). The incidence of grade 3 adverse events was 13.64%, with no grade 4 or higher events reported. Conclusions: The RC48 plus PD-1 inhibitor treatment regimen demonstrated clear antitumor activity and manageable safety in a multicenter real-world study of patients with La/mUC, with consistent therapeutic effects observed in patients with comorbidities.