Evidence-based management of hepatocellular carcinoma: systematic review and meta-analysis of randomized controlled trials (2002-2020)

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• dc.contributor.author Haber, Philipp K.
• dc.contributor.author Puigvehí, Marc
• dc.contributor.author Castet, Florian
• dc.contributor.author Lourdusamy, Vennis
• dc.contributor.author Montal, Robert
• dc.contributor.author Tabrizian, Parissa
• dc.contributor.author Buckstein, Michael
• dc.contributor.author Kim, Edward
• dc.contributor.author Villanueva, Augusto
• dc.contributor.author Schwartz, Myron
• dc.contributor.author Llovet, Josep Maria
• dc.date.accessioned 2022-02-25T07:02:33Z
• dc.date.issued 2021
• dc.description.abstract Background & aims: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with a rapidly changing landscape of treatments. In the past 20 years, numerous randomized controlled trials (RCTs) have aimed at improving outcomes across disease stages. We aimed to analyze the current evidence and identify potential factors influencing response to therapies. Methods: We conducted a systematic review of phase III RCTs (2002-2020) across disease stages. A meta-analysis was designed to examine the relationship between etiology and outcome after systemic therapies with either tyrosine-kinase inhibitor (TKI)/antiangiogenic or immune checkpoint inhibitor (ICI) therapy. Results: Out of 10,100 studies identified, 76 were phase III RCTs. Among them, a rigorous screening algorithm identified 49 with high quality including a total of 22,113 patients undergoing adjuvant (n = 7) and primary treatment for early (n = 2), intermediate (n = 7), and advanced (first-line, n = 21; second-line, n = 12) stages of disease. Nine of these trials were positive, 6 treatments have been adopted in guidelines (sorafenib [2 RCTs], lenvatinib, atezolizumab+bevacizumab, regorafenib, cabozantinib and ramucirumab), but 2 were not (adjuvant CIK cells and sorafenib plus hepatic arterial infusion with FOLFOX). Meta-analysis of 8 trials including 3739 patients revealed ICI therapy to be significantly more effective in patients with viral hepatitis compared with nonviral-related HCC, whereas no differences related to etiology were observed in patients treated with TKI/anti-vascular endothelial growth factor. Conclusions: Among 49 high-quality RCTs conducted in HCC during 2002-2020, 9 resulted in positive results. A meta-analysis of systemic therapies suggests that immunotherapies may be more effective in viral etiologies.
• dc.description.sponsorship PKH is supported by the fellowship grant of the German Research Foundation (DFG, HA 8754/1-1). MP received a "Juan Rodés" scholarship grant from Asociación Española para el Estudio del Hígado (AEEH). FC is supported by grant funding from Fundación Científica AECC. JML is supported by grants from the European Commission (EC) Horizon 2020 Program (HEPCAR, proposal number 667273-2), the US Department of Defense (CA150272P3), the National Cancer Institute (P30 CA196521), the Samuel Waxman Cancer Research Foundation, the Spanish National Health Institute (MICINN, SAF-2016-76390), through a partnership between Cancer Research UK, Fondazione AIRC and Fundación Científica de la Asociacion Española Contra el Cáncer (HUNTER, Ref. C9380/A26813), and by the Generalitat de Catalunya (AGAUR, SGR-1358).
• dc.format.mimetype application/pdf
• dc.identifier.citation Haber PK, Puigvehí M, Castet F, Lourdusamy V, Montal R, Tabrizian P, Buckstein M, Kim E, Villanueva A, Schwartz M, Llovet JM. Evidence-based management of hepatocellular carcinoma: systematic review and meta-analysis of randomized controlled trials (2002-2020). Gastroenterology. 2021;161(3):879-98. DOI: 10.1053/j.gastro.2021.06.008
• dc.identifier.doi http://dx.doi.org/10.1053/j.gastro.2021.06.008
• dc.identifier.issn 0016-5085
• dc.identifier.uri http://hdl.handle.net/10230/52572
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Gastroenterology. 2021;161(3):879-98
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/667273
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-76390
• dc.rights © Elsevier http://dx.doi.org/10.1053/j.gastro.2021.06.008
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Hepatocellular carcinoma
• dc.subject.keyword Liver cancer
• dc.subject.keyword Randomized controlled trials
• dc.subject.keyword Systematic review
• dc.title Evidence-based management of hepatocellular carcinoma: systematic review and meta-analysis of randomized controlled trials (2002-2020)
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion