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A systematic search of randomized clinical trials employing TKIs was performed in 17 databases, obtaining 25 studies evaluating the prognosis, tumor response, and presence of adverse events (AEs) related to TKIs in HCC. Overall effect sizes were estimated for the hazard ratios (HR) and odds ratios (OR) with 95% confidence interval (CI), either extracted or calculated with the Parmar method, employing STATA 16. Heterogeneity was assessed by Chi\u2010square\u2010based <jats:italic>Q<\/jats:italic>\u2010test and inconsistency (<jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>) statistic; source of heterogeneity by meta\u2010regression and subgroup analysis; and publication bias by funnel plot asymmetry and Egger's test. The research protocol was registered in PROSPERO (CRD42023397263). Meta\u2010analysis revealed a correlation between survival and tumor response parameters and TKI treatment vs. placebo, despite detecting high heterogeneity. Combined TKI treatment showed a significantly better objective response rate (ORR) with no heterogeneity, whereas publication bias was only detected with time to progression (TTP). Few gastrointestinal and neurological disorders were associated with TKI treatment vs. placebo or with combined treatment. However, a higher number of serious AEs were related to TKI treatment vs. sorafenib alone. Results show positive clinical benefits from TKI treatment, supporting the approval and maintenance of TKI\u2010based therapy for advanced HCC, while establishing appropriate strategies to maximize efficacy and minimize toxicity.<\/jats:p>","DOI":"10.1002\/cpt.3312","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T04:43:46Z","timestamp":1716871426000},"page":"328-345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Risk versus Benefit of Tyrosine Kinase Inhibitors for Hepatocellular Carcinoma: A\u00a0Systematic Review and Meta\u2010Analysis of Randomized Controlled Trials"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2245-6992","authenticated-orcid":false,"given":"Tania","family":"Payo\u2010Seraf\u00edn","sequence":"first","affiliation":[{"name":"Institute of Biomedicine (IBIOMED), Universidad de Le\u00f3n  Le\u00f3n Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6378-2554","authenticated-orcid":false,"given":"Carolina","family":"M\u00e9ndez\u2010Blanco","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (IBIOMED), Universidad de Le\u00f3n  Le\u00f3n Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9765-9562","authenticated-orcid":false,"given":"Paula","family":"Fern\u00e1ndez\u2010Palanca","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (IBIOMED), Universidad de Le\u00f3n  Le\u00f3n Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4954-7113","authenticated-orcid":false,"given":"Jennifer","family":"Mart\u00ednez\u2010Geijo","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (IBIOMED), Universidad de Le\u00f3n  Le\u00f3n Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8476-5489","authenticated-orcid":false,"given":"Mar\u00eda","family":"Reviejo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Instituto de Salud Carlos III  Madrid Spain"},{"name":"Experimental Hepatology and Drug Targeting (HEVEPHARM), IBSAL University of Salamanca  Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5664-5137","authenticated-orcid":false,"given":"Juan Jos\u00e9","family":"Ortiz\u2010de\u2010Urbina","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (IBIOMED), Universidad de Le\u00f3n  Le\u00f3n Spain"},{"name":"Pharmacy Service Complejo Asistencial Universitario de Le\u00f3n (CAULE), Hospital of Le\u00f3n  Le\u00f3n Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4386-9342","authenticated-orcid":false,"given":"Javier","family":"Gonz\u00e1lez\u2010Gallego","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (IBIOMED), Universidad de Le\u00f3n  Le\u00f3n Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1186-6849","authenticated-orcid":false,"given":"Jose J. 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