The Treatment Landscape of Advanced Hepatocellular Carcinoma

The systemic treatment of advanced hepatocellular carcinoma (HCC) has significantly evolved. Immune checkpoint inhibitors (ICIs) have demonstrated clinical efficacy and more favorable toxicity profiles compared to multikinase inhibitors. Combination therapy with ICIs may provide greater anti-tumor activity compared to ICI monotherapy. This review will discuss the current treatment landscape of advanced HCC, with a focus on recently completed and ongoing trials of ICI combinations, as well as future directions.  RECENT FINDINGS: Atezolizumab/bevacizumab has been approved as first-line therapy in patients with advanced HCC based on its superiority over sorafenib in the pivotal IMbrave150 trial. Similarly, durvalumab/tremelimumab demonstrated an improvement in overall survival compared to sorafenib in the HIMALAYA trial. Other combinations of ICIs with targeted agents and dual immune checkpoint blockade are currently being investigated in large randomized Phase 3 trials for the first-line treatment of HCC. Results of several ICI combination trials have been reported or are anticipated in the next few years and may potentially expand the therapy options in this patient population. Further areas of exploration include the use of ICIs in earlier stages of disease, other immunotherapy approaches such as adoptive T cell therapy, and the identification of predictive biomarkers. These ongoing efforts will likely further improve patient outcomes in the future.