Immune-Checkpoint Inhibitors in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. Prognosis is grim, with 5-year overall survival <10% for patients with advanced disease, and the management is complex, demanding a multidisciplinary approach. Recently, a better understanding of the pathophysiology and immune microenvironment of HCC has led to advances in systemic treatment with the incorporation of immunotherapeutic strategies. The rationale behind immunotherapy as a treatment modality for HCC include the immunosuppressive effects of chronic inflammatory conditions associated with cirrhosis and hepatitis. Initially, anti-PD-1 immune-checkpoint inhibitors (ICIs)—nivolumab and pembrolizumab—were evaluated in single-arm early-phase trials, with promising efficacy. However, larger confirmatory studies of anti-PD1 ICI alone have yielded disappointing results. This insufficient activity of single-agent ICI led to interest in combination strategies, and the association of atezolizumab (an anti-PD-L1 ICI) and bevacizumab (an anti-VEGF antibody) has been established as the new standard of care for first-line systemic therapy in advanced HCC. Furthermore, there is increasing interest in assessing the usefulness of ICIs as an option to earlier stages—either in the neoadjuvant or adjuvant settings or combined with locoregional approaches. In this chapter, we aim to review the rationale, efficacy data and future perspectives regarding the use of ICI for HCC.