Current Landscape of Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma

SIMPLE SUMMARY: Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy, with increasing incidence over the past several decades. The majority of patients with HCC present with advanced unresectable disease, making treatment options with curative intent limited and survival outlooks dismal. Systemic therapy with sorafenib had been traditionally used, with marginal benefit. Immunotherapy, successfully used to treat other malignant tumors, has recently been shown to be safe and well tolerated and to have promising long-term outcomes in patients with advanced HCC. We herein review the outcomes of immune checkpoint inhibitors (ICI) from major clinical trials, summarize predictors of treatment response, and highlight adverse events related to ICI treatment. ABSTRACT: Hepatocellular carcinoma (HCC) is the most frequent primary liver tumor. As a result of advanced disease being often present at diagnosis, only a small percentage of patients are amenable to curative-intent treatment options such as surgical resection and liver transplantation. Systemic therapy consisting of tyrosine kinase inhibitors such as sorafenib had been used for over a decade with limited efficacy. More recently, treatment with immune checkpoint inhibitors has revolutionized the treatment landscape of various malignant tumors. With this shifting paradigm, recent data have demonstrated encouraging outcomes among patients with HCC. In particular, several trials have investigated the safety and efficacy of various immune checkpoint inhibitors (ICI) either as monotherapy or in the form of combined treatments. We sought to provide an overview of recent clinical trials among patients with advanced HCC as well as to highlight predictors of response and immune-related adverse events and to review the evidence on perioperative administration of ICI in patients with resectable HCC.