Philipp K Haber1, Marc Puigvehí2, Florian Castet3, Vennis Lourdusamy1, Robert Montal4, Parissa Tabrizian1, Michael Buckstein1, Edward Kim1, Augusto Villanueva1, Myron Schwartz1, Josep M Llovet5. 1. Mount Sinai Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 2. Mount Sinai Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Hepatology Section, Gastroenterology Department, Parc de Salut Mar, Hospital del Mar Medical Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain. 3. Translational Research in Hepatic Oncology, Liver Unit, Instituto de Investigaciones Biomédicas August Pi i Sunyer, Hospital Clinic, University of Barcelona, Catalonia, Spain. 4. Cancer Biomarkers Research Group, Department of Medical Oncology, Hospital Universitari Arnau de Vilanova-IRBLleida, Lleida, Catalonia, Spain. 5. Mount Sinai Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Translational Research in Hepatic Oncology, Liver Unit, Instituto de Investigaciones Biomédicas August Pi i Sunyer, Hospital Clinic, University of Barcelona, Catalonia, Spain; Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain. Electronic address: josep.llovet@mssm.edu.
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.
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.
Authors: Josep M Llovet; Florian Castet; Mathias Heikenwalder; Mala K Maini; Vincenzo Mazzaferro; David J Pinato; Eli Pikarsky; Andrew X Zhu; Richard S Finn Journal: Nat Rev Clin Oncol Date: 2021-11-11 Impact factor: 65.011
Authors: Josep M Llovet; Roser Pinyol; Robin K Kelley; Anthony El-Khoueiry; Helen L Reeves; Xin Wei Wang; Gregory J Gores; Augusto Villanueva Journal: Nat Cancer Date: 2022-04-28
Authors: Scott M Thompson; Garima Suman; Michael S Torbenson; Zong-Ming E Chen; Danielle E Jondal; Anurima Patra; Eric C Ehman; James C Andrews; Chad J Fleming; Brian T Welch; Anil N Kurup; Lewis R Roberts; Kymberly D Watt; Mark J Truty; Sean P Cleary; Rory L Smoot; Julie K Heimbach; Nguyen H Tran; Amit Mahipal; Jun Yin; Tyler Zemla; Chen Wang; Zachary Fogarty; Mark Jacobson; Bradley J Kemp; Sudhakar K Venkatesh; Geoffrey B Johnson; David A Woodrum; Ajit H Goenka Journal: Hepatol Commun Date: 2021-11-15