Efficacy and safety of Disitamab Vedotin (RC48-ADC) monotherapy versus combination therapy with immune checkpoint inhibitors in solid tumors: a systematic review and meta-analysis

Background Combining antibody-drug conjugates (ADCs) with immune checkpoint inhibitors (ICIs) has emerged as a novel strategy to overcome immunotherapy resistance. This meta-analysis aims to systematically evaluate the efficacy and safety of Disitamab Vedotin (RC48) monotherapy versus combination therapy with ICIs in HER2-expressing advanced solid tumors, thereby validating its potential clinical benefits.Method We systematically searched multiple databases for relevant studies. Pooled ORs and HRs with 95% CIs were calculated for ORR (n = 320), DCR (n = 159), PFS (n = 300), OS (n = 70), and SAEs (n = 290).Results Seven studies involving 320 patients were included. Compared to monotherapy, the combination therapy yielded significantly superior efficacy, improving ORR (OR = 0.33, p < 0.05), DCR (OR = 0.42, p < 0.05), and, importantly, prolonging OS (HR = 0.46, p < 0.05). There was no statistically significant difference in PFS (HR = 0.91) or in the risk of grade ≥3 SAEs (OR = 0.77), indicating a manageable safety profile. Subgroup analysis highlighted that gastric cancer patients benefited most from combination therapy.Conclusion The RC48-ICI combination demonstrates robust clinical advantages over monotherapy in improving tumor response and OS without exacerbating severe toxicity. Our research results provide preliminary evidence that confirms the potential synergistic efficacy of this “ADC+immunotherapy” strategy. These findings are preliminary and hypothesis-generating, and require confirmation in prospective randomized trials.PROSPERO identification number PROSPERO CRD420251134291.