Recent Advances in Systemic Therapies for Advanced Hepatocellular Carcinoma

This paper aims to summarize the data of recently completed and key ongoing clinical trials of systemic agents for advanced hepatocellular carcinoma (aHCC). In particular, the review focuses on ongoing checkpoint inhibitor combination trials and promising studies combining tyrosine kinase inhibitors with checkpoint inhibitors.

The recently approved combination of atezolizumab and bevacizumab based on the IMbrave150 trial has shown the most potential with the highest overall survival of any systemic agent in HCC to date, surpassing sorafenib. Despite COVID-19 delays, other promising trials that involve combining VEGF-directed therapy and checkpoint inhibition, cancer vaccines, phosphatidylserine, YIV-906, and oncolytic and immunotherapeutic vaccinia virus are actively recruiting patients.

After almost a 10-year dormancy, the list of potential systemic treatment options for aHCC is growing rapidly. Given the promising data from the IMbrave150 trial, the combination of atezolizumab and bevacizumab is now the new first-line therapy. We discuss the change in landscape, the new second- and third-line systemic treatments in aHCC, and the ongoing clinical trials for newer agents including combination therapies.