Systemic Therapy for Hepatocellular Carcinoma: 2017 Update.

Systemic therapy for hepatocellular carcinoma (HCC) changed drastically after the introduction of the molecular targeted agent sorafenib in 2007. Sorafenib provides an additional therapeutic option for patients with extrahepatic spread or vascular invasion, resulting in improved survival even among patients with advanced HCC; however, the toxicity of sorafenib and its unsatisfactory antitumor effects remain unsolved issues. The development of novel molecular targeted agents as alternatives to sorafenib has been limited by difficulties unique to HCC. Recent studies have demonstrated the efficacy of two molecular targeted agents, the second-line agent regorafenib, which is used after sorafenib failure, and the first-line agent lenvatinib, which has been shown to be noninferior to sorafenib. Another category of agents that are attracting considerable interest are immune checkpoint inhibitors such as anti-PD-1/PD-L1 or CTLA-4 antibodies, which kill cancer cells via a unique mechanism. The therapeutic effects of some of these agents are currently under investigation in phase III studies. The most recent topics of interest are the combination of anti-PD-1/PD-L1 therapies with other immune checkpoint inhibitors, such as anti-CTLA-4 antibodies, or with a tyrosine kinase inhibitor, or with locoregional therapies such as resection, ablation, or transarterial chemoembolization.