| Systemic therapy for hepatocellular carcinoma (HCC) has changed markedly since the introduction of the molecular targeted drug sorafenib in 2007. Although sorafenib increased the available treatment options for extrahepatic spread and vascular invasion, and improved survival of patients with advanced HCC, various shortcomings such as low response rates and relatively high toxicity (e.g., hand–foot skin reaction) prompted concerted efforts to develop new molecular targeted agents and second-line drugs to treat those with disease progression or intolerance. Although many attempts to develop new drugs were made from about 2007 to 2016, all eight clinical trials conducted during this period failed. However, from 2017 through 2019, a total of four drugs (lenvatinib as a first-line agent and regorafenib, cabozantinib, and ramucirumab as second-line agents) emerged in quick succession from clinical trials and became available for clinical use. A recent phase 3 trial (IMbrave150) shows that combination immunotherapy with atezolizumab plus bevacizumab has improved overall survival above that of sorafenib therapy; worldwide approval is expected soon. In addition, treatment strategy for intermediate stage HCC is drastically changing by the introduction of the Lenvatinib-TACE sequential therapy for TACE unsuitable patient population. |
