Efficacy and safety of disitamab vedotin in patients with HER2-expressing locally advanced or metastatic urothelial carcinoma: A systematic review and meta-analysis.

Abstract

e16577 Background: Urothelial carcinoma (UC) is the 4th among most commonly diagnosed malignancy, notorious for poor outcomes in advanced stages, particularly in platinum-ineligible or immunotherapy-refractory patients. Disitamab vedotin (RC48-ADC), a HER2-targeted antibody-drug conjugate delivering monomethyl auristatin E, has shown activity in HER2-expressing UC. This meta-analysis synthesizes evidence on its efficacy and safety. Methods: A systematic search of PubMed, the Cochrane Library, and ClinicalTrials.gov was conducted through November 2025. Eligible studies included studies that assessed Disitamab vedotin (2.0 mg/kg IV every 2 weeks) as monotherapy or with PD-1 inhibitors in adults with HER2-expressing (IHC ≥1+) UC, locally advanced or metastatic in nature. Data were pooled using random-effects models for objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Heterogeneity was assessed using I², and risk of bias was assessed using the ROBINS-I tool. GRADE evaluated evidence certainty. Results: Seventeen studies with 880 patients (5 prospective trials, 12 observational cohorts) were included, with a median age of 65 years, 68% male population, and a median follow-up of 14.5 months. Pooled ORR was 54% (95% CI: 49%-59%; I² = 45.1%; n = 559). Pooled DCR was 84% (95% CI: 80%-88%; I² = 24.8%; n = 550), with partial response (44%; 95% CI: 39%-50%) and stable disease (29%; 95% CI: 24%-36%). Pooled median PFS was 7.47 months (95% CI: 6.06-8.87; 8 studies, n = 335; I² = 69.7%). OS data were limited to a pooled mean of 31.77 months. TRAEs included common events such as peripheral neuropathy (43%), fatigue (38%), decreased appetite (39%), and leukopenia (32%). The overall risk of bias for the majority of studies was judged as serious. Evidence certainty was moderate for ORR/DCR and low for PFS/safety. Conclusions: Disitamab vedotin demonstrates a favorable benefit: risk profile for antitumor activity in HER2-expressing advanced UC. Limitations include the non-randomized design and the predominantly Asian population, which limit generalizability. Nevertheless, these findings support the drug's promising role and highlight the need for larger-scale randomized trials.