{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:03:24Z","timestamp":1790053404132,"version":"4.0.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The FDA approval of immune checkpoint inhibitors for advanced gastroesophageal cancer (GEC) independent of programmed death-ligand 1 (PD-L1) expression status has sparked notable clinical controversy, highlighting the urgent need for evidence-based evaluation of the efficacy and safety of various PD-1 inhibitors combinations for this malignancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We followed the pre-registered PROSPERO protocol (CRD42022325401) to search the databases and conferences. The primary outcomes included overall survival (OS), progression-free survival (PFS), and treatment-related adverse event (TRAE). A random-effects model was applied for meta-analysis, with statistical data analysis performed using Review Manager software and the distribution of adverse event (AE) subtypes visualized via R software.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 6625 patients from 9 phase III randomized controlled trials (RCTs) were ultimately included in this analysis. The overall risk of included RCTs was low. Results found immunotherapy combined with chemotherapy improved patients\u2019 prognosis more than single-agent chemotherapy, with corresponding increased but manageable adverse effects. Subgroup analyses by drug type further revealed that sintilimab in combination with chemotherapy exhibited more efficacy than other PD-1 inhibitor-based regimens. The survival benefit in the immunotherapy combined with chemotherapy group compared to chemotherapy alone was seen in both PD-L1 CPS positive and TPS positive. The evidence strength was moderate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Findings from this comprehensive study confirm that immunotherapy combined with chemotherapy is more efficacious than traditional chemotherapy in the first-line treatment of patients with advanced unresectable GEC. Sintilimab combined with chemotherapy demonstrated favorable efficacy and safety profiles compared with other PD-1 therapies in terms of OS and PFS benefit without increasing TRAE base on indirect comparisons. The moderate evidence indicated PD-1 combined with chemotherapy may be a viable option for advanced unresectable GEC.<\/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 CRD42022325401.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1838929","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:23:48Z","timestamp":1790051028000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of PD-1 inhibitors plus chemotherapy for advanced unresectable gastroesophageal cancer: a systematic review and meta-analysis of phase III randomized controlled trials"],"prefix":"10.3389","volume":"16","author":[{"given":"Chenfeng","family":"Hua","sequence":"first","affiliation":[{"name":"Key Laboratory of Tobacco Chemistry, Zhengzhou Tobacco Research Institute of CNTC","place":["Zhengzhou, China"]},{"name":"Beijing Life Science Academy","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, the First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuli","family":"Mo","sequence":"additional","affiliation":[{"name":"Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanping","family":"Yan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tobacco Chemistry, Zhengzhou Tobacco Research 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