Immune checkpoint inhibitors plus trastuzumab and chemotherapy for the treatment of advanced HER2-positive gastric and gastroesophageal junction cancers: a systematic review and meta-analysis.

BACKGROUND

HER2-positive gastric and gastroesophageal junction (GEJ) cancers have poor prognosis despite standard trastuzumab-based chemotherapy. Immune checkpoint inhibitors (ICIs) may enhance therapeutic efficacy when combined with trastuzumab.

METHODS

A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Cochrane Library, Embase, and Scopus were searched up to December 29, 2025. Studies evaluating ICIs plus trastuzumab and chemotherapy versus trastuzumab-based therapy alone were included. Kaplan-Meier curves were digitized using WebPlotDigitizer and reconstructed to individual participant data (IPD). Pooled survival outcomes, objective response rate (ORR), disease control rate (DCR), and safety were analyzed.

RESULTS

Six studies including 1,097 patients were included. ICIs plus trastuzumab and chemotherapy significantly improved median progression-free survival (10.4 vs. 8.27 months; HR 0.6951, p<0.0001) and overall survival (20.4 vs. 17.2 months; HR 0.8104, p=0.004) compared with control. ORR (OR 1.85, p<0.00001) and DCR (OR 2.46, p=0.006) were also superior. Grade ≥3 adverse events were similar between groups.

CONCLUSIONS

ICIs combined with trastuzumab and chemotherapy improve survival and response rates in HER2-positive gastric/GEJ cancers with manageable toxicity, supporting their integration into treatment strategies.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420261280958.