Author information

¹Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, UC San Francisco, San Francisco, CA, USA. john.gordan@ucsf.edu.

²Quantitative Biosciences Institute, UC San Francisco, San Francisco, CA, USA. john.gordan@ucsf.edu.

³Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, UC San Francisco, San Francisco, CA, USA.

⁴Cancer Immunotherapy Program, Helen Diller Family Comprehensive Cancer Center, UC San Francisco, San Francisco, CA, USA.

⁵Quantitative Biosciences Institute, UC San Francisco, San Francisco, CA, USA.

⁶Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally and is rising in incidence. Until recently, treatment options for patients with advanced stages of HCC have been limited to antiangiogenic therapies with modest improvements in overall survival. The emerging role of immunotherapy with immune checkpoint inhibitors (ICI) in oncology has led to a rapid expansion in treatment options and improvements in outcomes for patients with advanced stages of HCC. Recent clinical trials have shown meaningful survival improvement in patients treated with the combination of bevacizumab and atezolizumab, as well as with the combination of tremelimumab with durvalumab, resulting in regulatory approvals of these regimens as frontline therapy. Beyond improvements in overall survival, ICI-based combination regimens achieve higher rates of durable treatment response than multikinase inhibitors and have favorable side effect profiles. With the emergence of doublet anti-angiogenic and immune checkpoint inhibitor (ICI) and dual ICI combinations, individualized therapy is now possible for patients based on co-morbidity profiles and other factors. These more potent systemic therapies are also being tested in earlier stages of disease and in combination with loco-regional therapies such as trans-arterial chemoembolization and stereotactic body radiotherapy. We summarize these advances and emerging therapeutic combinations currently in clinical trials.