Evolving Systemic Therapy in Hepatocellular Carcinoma: Current Management and Opportunities for Integration With Radiotherapy

The majority of patients with hepatocellular carcinoma (HCC) present with advanced disease. While first-line therapy with sorafenib is considered standard of care for patients with advancedHCC, outcomes remain poor. Despite early evidence of antitumor activity from Phase II trials of multiple other tyrosine kinase inhibitors, Phase III trials have largely failed to show an improvement insurvival outcomes over sorafenib. Given the encouraging early results with liver-directed radiotherapy for patients with advanced HCC, there is an increased interest in combination of these therapies tooptimize patient outcomes and improve survival by maximizing both local and distant disease control. Phase II trials of checkpoint inhibitors in HCC have also reported encouraging results, and Phase IIItrials are ongoing. Trials of combining radiotherapy with immunotherapy in solid tumors have shown intriguing results, potentially reflecting the opportunity for synergistic effects with the use of both modalities.