Systemic therapy for hepatocellular carcinoma: Recent advances

Abstract

Systemic therapy for hepatocellular carcinoma has markedly advanced since the survival benefit of a molecular target agent, sorafenib, were demonstrated in the SHARP and Asia Pacific trials in 2007. Treatment options for extrahepatic spread and/or vascular invasion increased, and long-term survival for patients with advanced stage hepatocellular carcinoma has become possible to some extent. However, development of a first-line novel molecular target agent substituting for sorafenib and a second-line agent after disease progression on or intolerant to sorafenib has been desired because sorafenib lacks tumor size-reducing/necrotizing effects and induces relatively severe adverse events such as hand foot skin reaction. Many agents were attempted to develop between 2007 and 2016, but all of these clinical trials failed. On the other hand, clinical trials of 4 agents (regorafenib, lenvatinib, cabozantinib, and ramucirumab) succeeded in succession in 2017 and 2018, and their use in clinical practice is possible (regorafenib and Lenvatinib) or underway (cabozantinib and ramucirumab). Phase 3 clinical trials of immune checkpoint inhibitors and a combination therapy of immune checkpoint inhibitors and molecular targeted agents are also ongoing, which suggests treatment paradigm of hepatocellular carcinoma is expected to be changed drastically.