Systemic Therapy for Advanced Hepatocellular Carcinoma in an Evolving Landscape.

OPINION STATEMENT: Globally, hepatocellular carcinoma (HCC) is a leading cause of cancer-related death and a malignancy with rising incidence. After sorafenib remaining the one and only FDA-approved therapy for the disease for many years, the past 2 years has seen the landscape of available treatments change dramatically. Multiple multi-targeted tyrosine kinases (TKIs) have demonstrated success and garnered FDA approval both in the first- (lenvatinib) and second-line (regorafenib) settings. Now, various questions regarding the sequencing of these therapies remain for investigation. Effective positioning of these TKIs will be crucial to optimization of outcomes for patients with HCC. Additionally, promising outcomes have been seen with a number of immunotherapies, and one such agent has been approved (nivolumab). Positioning of these immunotherapies in the landscape may or may not have impacts upon sequencing of all of the available therapies. Further studies are ongoing investigating such sequencing questions, in addition to more novel agents to combat this devastating disease.