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Abstract Details
Evidence-based management of HCC: Systematic review and meta-analysis of randomized controlled trials (2002-2020)
Gastroenterology. 2021 Jun 11;S0016-5085(21)03119-X. doi: 10.1053/j.gastro.2021.06.008.Online ahead of print.
Philipp K Haber1, Marc Puigvehí2, Florian Castet3, Vennis Lourdusamy1, Robert Montal4, Parissa Tabrizian1, Michael Buckstein1, Edward Kim1, Augusto Villanueva1, Myron Schwartz1, Josep M Llovet5
Author information
1Mount Sinai Liver Cancer Program, [Division of Liver Diseases, RMTI, Dept of Radiology, Hematology/Medical Oncology,] Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
2Mount Sinai Liver Cancer Program, [Division of Liver Diseases, RMTI, Dept of Radiology, Hematology/Medical Oncology,] Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Hepatology Section, Gastroenterology Department, Parc de Salut Mar, IMIM (Hospital del Mar Medical Research Institute), Universitat Autònoma de Barcelona, Barcelona, Spain.
3Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Catalonia, Spain.
4Department of Medical Oncology, Cancer Biomarkers Research Group, Hospital Universitari Arnau de Vilanova - IRBLleida, Lleida, Catalonia, Spain.
5Mount Sinai Liver Cancer Program, [Division of Liver Diseases, RMTI, Dept of Radiology, Hematology/Medical Oncology,] Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Catalonia, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain. Electronic address: josep.llovet@mssm.edu.
Abstract
Background and 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 (RCT) have aimed at improving outcomes across disease stages. We aimed at analyzing the current evidence and identifying potential factors influencing response to therapies.
Methods: We conducted a systematic review of phase III RCTs across disease stages (2002-2020). Meta-analysis was designed to examine the relationship between etiology and outcome after systemic therapies with either tyrosine-kinase inhibitor/antiangiogenic or immune checkpoint inhibitors (ICI) therapy.
Results: Out of 10,100 studies identified, 76 were phase III RCT. 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 stage disease (first-line, n=21; second-line, n=12). Nine of these trials were positive, six treatments have been adopted in guidelines [sorafenib (2 RCTs), lenvatinib, atezolizumab+bevacizumab, regorafenib, cabozantinib and ramucirumab] but two did not (adjuvant CIK cells and sorafenib-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 when compared with non-viral related HCC whereas no differences related to etiology were observed in patients treated with TKI/anti-VEGF.
Conclusions: Among 49 high-quality RCTs conducted in HCC during 2002-2020, nine resulted in positive results. A meta-analysis of systemic therapies suggest that immunotherapies may be less effective in non-viral etiologies.