The efficacy and safety of disitamab vedotin plus immunotherapy in locally advanced or metastatic urothelial carcinoma: A systematic review and meta-analysis.

Abstract

774 Background: The combination of disitamab vedotin (DV), a novel human epidermal growth factor receptor 2 (HER2)-targeting antibody-drug conjugate, with immunotherapy represents a promising strategy for locally advanced or metastatic solid tumors. However, comprehensive evidence regarding its efficacy and safety in locally advanced or metastatic urothelial carcinoma is lacking. Therefore, this systematic review and meta-analysis aimed to synthesize available data about the combination regimen in this population. Methods: We systematically searched PubMed, Scopus, Embase, and the Cochrane Library for studies published up to September 1, 2025. The primary outcomes were objective response rate (ORR) and treatment-related adverse events (TRAEs). Secondary outcomes included disease control rate (DCR) and median progression-free survival (mPFS). Pooled analyses were performed using a random-effects model. Results: Eleven studies involving 517 patients were included. The pooled ORR was 57% (95% CI: 50%–64%), and the DCR was 86% (95% CI: 80%–90%). The pooled mPFS was 8.2 months (95% CI: 6.7–9.7). Subgroup analyses indicated superior efficacy in HER2-positive tumors, and first-line treatment settings. Any-grade and grade ≥3 TRAEs occurred in 87.5% and 26.4% of patients, respectively, with a toxicity profile dominated by DV-related adverse events such as fatigue, hypoaesthesia, and hematological toxicities. Conclusions: The combination of DV and immunotherapy demonstrates encouraging antitumor activity and a manageable safety profile in patients with locally advanced or metastatic urothelial carcinoma, particularly in HER2-expressing populations and when used in the first-line setting. These findings support further investigation of this combination in randomized controlled trials.