{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T08:33:38Z","timestamp":1761294818925,"version":"3.41.2"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"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><jats:title>Background<\/jats:title><jats:p>Hepatic arterial infusion chemotherapy (HAIC) is increasingly recognized as a primary treatment option for patients with unresectable hepatocellular carcinoma (uHCC), providing a focused treatment for localized tumors. The combination of lenvatinib, a multikinase inhibitor, with PD-1 inhibitors has demonstrated significant survival benefits in HCC. This meta-analysis aims to assess whether the integration of HAIC with lenvatinib and PD-1 inhibitors (referred to as the HAIC-L-P group) leads to better treatment effectiveness and security compared to lenvatinib and PD-1 inhibitors alone (L-P group) in uHCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An exhaustive search of the literature was conducted, including PubMed, the Cochrane Library, Embase, ClinicalTrials.gov, and Web of Science, from the start of each database until September 2024, to ensure a thorough and up-to-date compilation of relevant studies. Extract data on outcome measures such as overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Subsequently, meta-analyses were performed using RevMan 5.4 to quantitatively evaluate the aggregated effect of the HAIC-L-P regimen versus the L-P regimen alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In our systematic meta-analysis of eight retrospective cohort studies, the HAIC-L-P regimen demonstrated markedly enhanced OS, with an HR of 0.54 (95% CI: 0.45-0.64; p &amp;lt; 0.00001), and enhanced 1-year and 2-year OS rates. Superior PFS was also observed in the HAIC-L-P group, with an HR of 0.64 (95% CI: 0.55-0.75; p &amp;lt; 0.0001), and higher 1-year and 2-year PFS rates. Response rates were markedly higher in the HAIC-L-P group, with an ORR risk ratio of 2.15 (95% CI: 1.84-2.50; p &amp;lt; 0.00001) and a DCR risk ratio of 1.28 (95% CI: 1.20-1.43; p &amp;lt; 0.0001). The AEs classified as grade 3 or above were elevated in the HAIC-L-P group, with notable risk ratios for vomiting, elevated AST, elevated ALT, thrombocytopenia, neutropenia, and hyperbilirubinemia. No life-threatening AEs were reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The HAIC-L-P regimen correlated with enhanced tumor responses and prolonged survival, alongside manageable adverse effects, indicating its potential as a viable therapeutic strategy for individuals afflicted with uHCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic review registration<\/jats:title><jats:p><jats:uri>https:\/\/www.crd.york.ac.uk\/PROSPERO\/<\/jats:uri>, identifier CRD42024594109.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1513394","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T07:25:50Z","timestamp":1739345150000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Enhanced antitumor activity of combined hepatic arterial infusion chemotherapy with Lenvatinib and PD-1 inhibitors in unresectable hepatocellular carcinoma: a 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