Biologic and Immunotherapy Developments in Advanced Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver, and the second leading cause of cancer-related mortality worldwide with a very poor 5-year survival. Treatment for HCC includes surgery, liver-directed therapies and systemic therapies. Until 2008, no effective systemic therapy was available for advanced HCC. Sorafenib is the first drug to show improvement in overall survival among patients with advanced HCC in comparison to placebo, and it is approved by U.S. Food and Drug Administration (FDA) as a first-line treatment of advanced HCC. After sorafenib approval, several targeted and immune therapies were tested and showed efficacy in advanced HCC. Lenvatinib has been shown to be non-inferior to sorafenib as first-line treatment. Both nivolumab and regorafenib showed improvement in overall survival among patients with advanced HCC as a second line treatment after progression on sorafenib, and both are FDA approved for this indication. There is a limited role for cytotoxic agents in the treatment of advanced HCC.