Immune checkpoint blockade in advanced hepatocellular carcinoma: an update and critical review of ongoing clinical trials

Systemic treatments for advanced hepatocellular carcinoma (HCC) are evolving rapidly and several multi-targeted tyrosine kinase inhibitors have demonstrated a survival advantage over best supportive care. Despite these treatment advances, the majority of HCC patients will progress on tyrosine kinase inhibitor therapy. Preclinical data indicate that interference with immune checkpoint molecules results in HCC growth suppression. Several clinical trials applying monoclonal antibodies to immune checkpoint molecules have demonstrated durable antitumor activity in advanced HCC patients. As such, pivotal clinical trials are now in progress to assess if these agents will alter the natural history of the disease and further extend the overall survival of advanced HCC patients. This manuscript will review the current status of immune checkpoint blockade in patients with advanced HCC.