Efficacy of disitamab vedotin-based therapy in HER2-negative and HER2-low locally advanced or metastatic urothelial carcinoma: A systematic review and meta-analysis.

While disitamab vedotin (DV) shows promising efficacy in HER2-positive locally advanced/metastatic urothelial carcinoma (la/mUC), its clinical efficacy in HER2-negative and HER2-low (immunohistochemistry [IHC] 0 and 1+) populations is unclear. This meta-analysis aims to evaluate DV-based therapy in these underserved subgroups. PubMed, Scopus, Embase, and Cochrane were main databases when searching articles published from January 2000 to December 2025 (PROSPERO: CRD420251130969). Primary endpoints were objective response rate (ORR) and median progression-free survival (mPFS). Secondary endpoints included disease control rate (DCR) and median overall survival (mOS). Random-effects models assessed pooled effects, with subgroup analyses by HER2 expression. Nonrandomized studies of interventions version I tool (ROBINS-I) was used to evaluate the risk of bias. 16 studies with 279 HER2-negative and HER2-low la/mUC cases were included. DV-based therapy achieved an ORR of 51% (95% confidence interval [CI], 44%-57%), DCR of 75% (95% CI, 63%-84%), and mPFS of 5.48 (95% CI, 4.99-5.97) months, with better outcomes in HER2-low (ORR, 55%; 95% CI, 48%-63%) versus HER2-negative (ORR, 34%; 95% CI, 22%-49%) subgroups. Insufficient available data precluding formal meta-analytic synthesis of mOS. Limitations include small sample size and the inability to perform in-depth subgroup analyses. This study establishes the first comprehensive evidence for the clinical efficacy of DV-based therapy in HER2-negative and HER2-low la/mUC, providing a foundation for expanding DV applications in biomarker-selected la/mUC patients. Future high-quality studies are warranted to further elucidate the clinical efficacy of DV-based therapy in this patient population.