Systemic therapy for hepatocellular carcinoma, from the early to the advanced stage: a Japanese perspective

Systemic therapy has now become mainstream for the treatment of hepatocellular carcinoma (HCC) and is also changing from molecular-targeted therapy, such as with sorafenib and lenvatinib, to immunotherapy, such as with the atezolizumab plus bevacizumab and durvalumab plus tremelimumab combination regimens. Molecular-targeted therapy is selected as the first-line treatment when immunotherapy is not indicated or as second- or later-line treatment when immunotherapy is ineffective. It is necessary to select the appropriate treatment taking into consideration the expected treatment efficacy and adverse events, as well as the hepatic reserve. Currently, newer agents and combination regimens as first-line/second-line treatment for advanced-stage HCC, combined therapy with transarterial chemoembolization for intermediate-stage HCC, and perioperative adjuvant therapy for curative treatment for early-stage HCC are being developed. Therefore, systemic therapy is now indicated for any stage of the disease. While local therapies were previously used as the main treatment strategy for HCC, systemic therapy in combination with local therapies is being actively attempted at present. Systemic therapy is currently the main focus of development of novel treatments for HCC.