{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T21:25:55Z","timestamp":1788989155017,"version":"build-2803163510"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"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>Introduction<\/jats:title>\n                    <jats:p>This meta-analysis was designed to compare the long-term outcomes of first-line programmed cell death protein 1 (PD-1) inhibitors plus chemotherapy versus chemotherapy in patients with advanced HER2-negative gastric cancer (GC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Four databases (PubMed, Embase, Web of Science, and the Cochrane Library) were searched for randomized controlled trials (RCTs) comparing first-line PD-1 inhibitors plus chemotherapy to chemotherapy in patients with advanced HER2-negative GC. The search was conducted from the databases establishment to October 11, 2025. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), treatment-related adverse events (TRAEs), and Grade\u22653 TRAEs were subjected to meta-analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Six RCTs were included in the meta-analysis. The meta-analysis included a group of 6038 patients diagnosed with untreated advanced HER2-negative GC. Within this cohort, 3026 patients were administered first-line PD-1 inhibitors together with chemotherapy, while 3012 patients received first-line chemotherapy alone. Compared with chemotherapy, first-line PD-1 inhibitors plus chemotherapy yielded superior OS (HR = 0.91; 95% CI 0.89 to 0.93; P&amp;lt;0.01), PFS (HR = 0.89, 95%CI 0.87 to 0.91 P&amp;lt;0.01), and ORR (RR = 1.22, 95% CI, 1.16 to 1.29, P&amp;lt;0.01). With regards to safety, first-line PD-1 inhibitors plus chemotherapy exhibited a greater likelihood of encountering TRAEs (RR = 1.02, 95% CI: 1.00 to 1.04, P = 0.03) and Grade\u22653 TRAEs (RR = 1.16, 95% Cl: 1.08 to 1.25, P&amp;lt;0.01) in comparison to chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Compared with chemotherapy alone, PD-1 inhibitors plus chemotherapy as first-line therapy provided improved OS, PFS, and ORR. Furthermore, the heightened efficacy of PD-1 inhibitors plus chemotherapy was accompanied by a rise in TRAEs and Grade\u22653 TRAEs.<\/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 CRD420251015248.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1651176","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T11:45:27Z","timestamp":1763466327000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Long-term outcomes of PD-1 inhibitors plus chemotherapy as first-line treatment for advanced HER2-negative gastric cancer: an updated systematic review and 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