Recent advances in systemic therapy for hepatocellular carcinoma

Abstract

Abstract For the treatment of advanced hepatocellular carcinoma (HCC), phase III trials have shown that sorafenib and lenvatinib as first-line treatment agents, and regorafenib, ramcirumab, and cabozantinib as subsequent-line treatment agents in combination with sorafenib, offer survival benefit. At present, sorafenib and lenvatinib for patients with advanced HCC, and regorafenib for patients who are refractory to systemic therapy are reimbursed and can be available in Japan. In the near future, ramucirumab is also expected to be approved for further treatment after second-line treatment of HCC patients with serum AFP levels of 400 ng/mL or more, and data on cabozantinib are also expected to be submitted for approval. Furthermore, the efficacy of immune checkpoint inhibitors is also expected. In regard to the anti-PD-1 antibody, nivolumab, patient enrollment for a phase III trial has been completed in a phase III study initiated to compare sorafenib and nivolumab in a first-line setting, and the final results are expected. A phase III trial conducted to compare pembrolizumab and placebo in sorafenib-refractory/intolerant patients revealed that pembrolizumab offered no survival benefit. However, the drug may be expected to be effective when used in combination with other agents. Currently, trials of combined immune checkpoint inhibitor plus immune checkpoint inhibitor and combined immune checkpoint inhibitor plus molecular-targeted agent therapy are ongoing, while some phase III trials have already been completed. In this session, current evidence on systemic therapy for advanced HCC will be reviewed and the trends in the future development of treatments for HCC will be outlined.