Systemic treatment of hepatocellular carcinoma: standard of care in China and elsewhere

Hepatocellular carcinoma is the fifth most common cancer and second leading cause of cancer-related death globally. More than half of all patients are in China. For nearly 10 years, sorafenib was the only drug to have shown survival benefit in advanced hepatocellular carcinoma. 1 Llovet JM Ricci S Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008; 359: 378-390 Crossref PubMed Scopus (9037) Google Scholar , 2 Cheng AL Kang YK Chen Z et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009; 10: 25-34 Summary Full Text Full Text PDF PubMed Scopus (4450) Google Scholar Regorafenib, lenvatinib, cabozantinib, and ramucirumab have given positive results in phase 3 trials. From 2008 to 2017, however, many phase 3 trials testing new drugs in first or second lines failed, despite promising results observed in the early phases. Reasons for those failures have been discussed previously: poor understanding of drivers of progression, flaws in trial design, underestimation of liver toxicity, marginal antitumour activity, and an absence of trial enrichment with adequate biomarkers of benefit. 3 Llovet JM Hernandez-Gea V Hepatocellular carcinoma: reasons for phase III failure and novel perspectives on trial design. Clin Cancer Res. 2014; 20: 2072-2079 Crossref PubMed Scopus (308) Google Scholar Many histology-based, molecular-based or immune-based classifications have now been published to assist that enrichment. 4 Llovet JM Montal R Sia D Finn RS Molecular therapies and precision medicine for hepatocellular carcinoma. Nat Rev Clin Oncol. 2018; 15: 599-616 Crossref PubMed Scopus (927) Google Scholar Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trialCamrelizumab showed antitumour activity in pretreated Chinese patients with advanced hepatocellular carcinoma, with manageable toxicities, and might represent a new treatment option for these patients. Full-Text PDF