Immune checkpoint inhibitors in hepatocellular carcinoma: emerging challenges in clinical practice

Systemic therapy for advanced hepatocellular carcinoma has expanded at an unprecedented pace over the past 5 years. After tyrosine kinase inhibitors dominated the field for more than a decade, immune checkpoint inhibitor (ICI)-based therapies have become the main component in systemic first-line treatment of this cancer. Delivery of immunotherapy in routine clinical practice recognises several challenges. In this Viewpoint, we discuss the major gaps in knowledge around the role of ICI-based therapies in patients with Child-Pugh class B. We discuss the challenges in individuals with rare histological subtypes of primary liver cancer, including combined hepatocellular-cholangiocarcinoma, fibrolamellar hepatocellular carcinoma, and sarcomatoid hepatocellular carcinoma. We also review data on ICI rechallenge in patients previously treated with ICIs, and discuss atypical patterns of progression related to immunotherapy (ie, hyperprogressive disease and pseudoprogression).