{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:01:53Z","timestamp":1789682513139,"version":"4.0.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013254","name":"National College Students Innovation and Entrepreneurship Training Program","doi-asserted-by":"publisher","award":["2025\u5e74\u7701\u7ea7\u521b\u65b0\u57f9\u8bad\u8ba1\u5212\uff08\u7b2c202510062044\u671f\uff09"],"award-info":[{"award-number":["2025\u5e74\u7701\u7ea7\u521b\u65b0\u57f9\u8bad\u8ba1\u5212\uff08\u7b2c202510062044\u671f\uff09"]}],"id":[{"id":"10.13039\/501100013254","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Immune checkpoint inhibitor (ICI) monotherapy has shown limited efficacy in PDAC, whereas the potential clinical value of first-line ICI-based combination regimens remains unclear. Through a systematic review and meta-analysis, this study aimed to evaluate the efficacy and safety of first-line ICI-based combination regimens in advanced PDAC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Embase, The Cochrane Library, Scopus, Web of Science, CNKI, Wanfang Data, VIP, and CBM were searched up to April 4, 2026, to identify clinical studies evaluating first-line ICI-based combination therapy for advanced PDAC. Study screening and data extraction were performed in accordance with PRISMA guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eight clinical trials involving 379 patients were included. In RCT-only analyses, ICI-based combination regimens showed favorable but statistically non-definitive trends for OS (HR\u00a0=\u00a00.83, 95% CI: 0.65-1.06) and PFS (HR\u00a0=\u00a00.75, 95% CI: 0.53-1.05), while ORR was improved (OR\u00a0=\u00a02.19, 95% CI: 1.32-3.64). Single-arm pooled analysis showed a median PFS of 6.2 months and an ORR of 38.0%. In terms of safety, combination therapy increased the risk of specific Grade 3 or higher adverse events, but the overall incidence was clinically manageable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>First-line ICI-based combination regimens showed encouraging antitumor activity in advanced PDAC, particularly for radiological response. However, definitive survival benefits were not established in RCT-only analyses, and further large-scale randomized trials are needed.<\/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\/view\/CRD420261440306<\/jats:ext-link>\n                      , identifier CRD420261440306.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1855859","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:37:31Z","timestamp":1783661851000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Advancing precision immunotherapy in advanced pancreatic cancer: a systematic review and meta-analysis of first-line ICI-based 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