{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:52:27Z","timestamp":1782910347422,"version":"3.54.5"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2013Meier 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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&amp;lt;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&amp;lt;0.00001) and DCR (OR 2.46, p=0.006) were also superior. Grade \u22653 adverse events were similar between groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>\n                      , identifier CRD420261280958.\n                    <\/jats:p>\n                  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