{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:56:32Z","timestamp":1787241392029,"version":"build-2736575974"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T00:00:00Z","timestamp":1697414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\n Background<\/jats:title>\n The triple combination of hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitors (ICIs) is expected to have a synergistic anticancer effect in HCC. We conducted this meta-analysis to evaluate the efficacy and safety of the triple combination treatment in advanced HCC patients.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n PubMed, Embase, Cochrane Library, Web of Science databases were systematically searched for relevant studies from the inception of each database to May 10, 2023. All articles focusing the triple combination treatment of HAIC-FO plus TKI and ICIs for advanced HCC were eligible. The meta-analysis was conducted following the PRISMA guidelines. The risk of bias was assessed using the Joanna Briggs Institute (JBI) for case series and Newcastle-Ottawa Scale (NOS) for cohort studies. The primary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). The secondary results were adverse events. Further meta-analysis of control studies demonstrated the superiority of the triple combination modality to TKI plus ICIs, and TKI alone.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Nine articles (four cohort studies and five one-arm studies) involving 777 advanced HCC patients were included in this meta-analysis. In terms of survival analysis, the pooled median PFS was 11 months (95% CI: 10.1\u201312.0 months) with low heterogeneity (I\n 2<\/jats:sup>\n = 0%,\n p<\/jats:italic>\n = 0.97). With regard to tumor response, the pooled ORR and DCR was 61.6% (I\n 2<\/jats:sup>\n =0%,\n p<\/jats:italic>\n = 0.71) and 87.9% (I\n 2<\/jats:sup>\n = 13%,\n p<\/jats:italic>\n = 0.33) with low heterogeneity, respectively. As compared with TKIs plus ICIs, and TKIs alone, the triple combination thrapy was associated with improved median OS (HR=0.51, 95%CI 0.41-0.62) with low heterogeneity across studies (I\n 2<\/jats:sup>\n = 0%,\n p<\/jats:italic>\n = 0.47), median PFS (HR=0.51, 95%CI 0.41-0.64) with low heterogeneity across studies (I\n 2<\/jats:sup>\n = 0%,\n p<\/jats:italic>\n = 0.41), ORR (RR = 0.56, 95% CI: 0.42\u20130.74) with high heterogeneity across studies (I\n 2<\/jats:sup>\n = 69%,\n p<\/jats:italic>\n = 0.02), and DCR (RR = 0.38, 95%CI 0.27\u20130.54) with low heterogeneity across studies (I\n 2<\/jats:sup>\n = 14%,\n p<\/jats:italic>\n = 0.32). The most common 3\/4 AEs were elevated ALT and AST, thrombocytopenia, hypertension, nausea and vomiting in this meta-analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The triple combination therapy of HAIC-FO plus TKI and ICIs showed promising efficacy and safety in patients with advanced HCC.<\/jats:p>\n <\/jats:sec>\n \n Registration<\/jats:title>\n \n The protocol was registered with PROSPERO (ID:\n CRD42023424281<\/jats:ext-link>\n ).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0290644","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T13:27:18Z","timestamp":1697462838000},"page":"e0290644","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Triple combination of HAIC-FO plus tyrosine kinase inhibitors and immune checkpoint inhibitors for advanced hepatocellular carcinoma: A systematic review and meta-analysis"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5739-9233","authenticated-orcid":true,"given":"Zhongbao","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4470-7989","authenticated-orcid":true,"given":"Lan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanjing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuequn","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhai","family":"Di","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daguang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,10,16]]},"reference":[{"key":"pone.0290644.ref001","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"pone.0290644.ref002","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.jhep.2021.11.018","article-title":"BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update","volume":"76","author":"M Reig","year":"2022","journal-title":"J Hepatol"},{"key":"pone.0290644.ref003","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1200\/JCO.21.00608","article-title":"Hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin versus transarterial chemoembolization for large hepatocellular carcinoma: A randomized phase III trial","volume":"40","author":"QJ Li","year":"2022","journal-title":"J Clin Oncol"},{"key":"pone.0290644.ref004","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1111\/jgh.15010","article-title":"Systematic review of hepatic arterial infusion chemotherapy versus sorafenib in patients with hepatocellular carcinoma with portal vein tumor thrombosis","volume":"35","author":"M Liu","year":"2020","journal-title":"J Gastroenterol Hepatol"},{"key":"pone.0290644.ref005","doi-asserted-by":"crossref","first-page":"849189","DOI":"10.3389\/fphar.2022.849189","article-title":"Cost-Effectiveness Analysis of Hepatic Arterial Infusion Chemotherapy of Infusional Fluorouracil, Leucovorin, and Oxaliplatin Versus Transarterial Chemoembolization in Patients With Large Unresectable Hepatocellular Carcinoma","volume":"13","author":"H Zhang","year":"2022","journal-title":"Front Pharmacol"},{"key":"pone.0290644.ref006","unstructured":"Chinese Society of Clinical Oncology (CSCO). 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