Immunotherapy Updates in Advanced Hepatocellular Carcinoma

SIMPLE SUMMARY: Advanced hepatocellular carcinoma (HCC) carries a grim prognosis, which has historically been compounded by a lack of available systemic therapies. Sorafenib monotherapy was the standard of care for front-line treatment of advanced HCC for many years, despite both poor tolerability and lack of durable responses. In the past few years, there have been several clinical trials evaluating the efficacy of immune checkpoint inhibitors for advanced HCC. Use of immune checkpoint inhibitors alone, and in combination with targeted therapies, has led to improved outcomes in both treatment-naïve and subsequent line treatment of advanced HCC. Here we review the role of immunotherapy in the treatment of HCC, describe the mechanistic basis for combination with targeted therapy, and summarize the recent published data as well as ongoing clinical trials for the use of immunotherapy in the treatment of advanced HCC. ABSTRACT: Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide. HCC tumor development and treatment resistance are impacted by changes in the microenvironment of the hepatic immune system. Immunotherapy has the potential to improve response rates by overcoming immune tolerance mechanisms and strengthening anti-tumor activity in the tumor microenvironment. In this review, we characterize the impact of immunotherapy on outcomes of advanced HCC, as well as the active clinical trials evaluating novel combination immunotherapy strategies. In particular, we discuss the efficacy of atezolizumab and bevacizumab as demonstrated in the IMbrave150 study, which created a new standard of care for the front-line treatment of advanced HCC. However, there are multiple ongoing trials that may present additional front-line treatment options depending on their efficacy/toxicity results. Furthermore, the preliminary data on the application of chimeric antigen receptor (CAR-T) cell therapy for treatment of HCC suggests this may be a promising option for the future of advanced HCC treatment.