Current Landscape of Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma

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.

A Differentiation-Related Gene Prognostic Index Contributes to Prognosis and Immunotherapy Evaluation in Patients with Hepatocellular Carcinoma

“…Some studies have shown that the objective remission rate (ORR) of ICIs for hepatocellular carcinoma is about 17–20% [ 7 ], and their ORR is low, so it is vital to discover predictive markers for the benefit of ICI therapy [ 8 ]. However, due to the complexity and diversity of the tumor immune microenvironment, immunotherapy or combined immunotherapy has not fundamentally changed the therapeutic outcome of patients with HCC [ 9 ], and there is a lack of biomarkers to predict the outcome of ICI therapy [ 10 , 11 ]. Therefore, it is extremely urgent to understand the composition and characteristics of the HCC immune microenvironment and to find biomarkers that can predict the benefit of ICI therapy in patients with HCC, which will also provide a favorable basis for individualized ICI therapy for patients with HCC.…”

Blood-based biomarkers for immune-based therapy in advanced HCC: Promising but a long way to go

“…Over the past ten years, several clinical trials have demonstrated the contribution of ICIs to the improvement of overall survival (OS) of patients with various tumors. Notably, immunotherapies are generally safe and well-tolerated by patients ( 16 ); however, under some circumstances, ICI therapy can cause serious adverse events (AEs), resulting in discontinuation and disease hyper-progression in some cases ( 17 ). It is critical to identify reliable biomarkers that would facilitate the selection of patients who will be responsive to ICI treatment as well as those likely to suffer serious AEs.…”

“…Molecular biomarkers are prevalent in the blood or tissues ( 18 ). Several putative biomarkers are being evaluated in clinical trials for ICI therapy against HCC, including programmed death ligand-1 (PD-L1) expression, microsatellite instability (MSI), tumor mutational burden (TMB), DNA damage repair gene alterations, gut microbiome, and various blood biomarkers ( 16 , 19 ). Among these, markers in blood samples are easily measured and can serve as tools for clinical management, diagnosis, staging, and evaluation of therapeutic response ( 18 ).…”

Meta-Analysis of Repeat Hepatectomy versus Radiofrequency Ablation for Recurrence of Hepatocellular Carcinoma

“…Hepatocellular carcinoma (HCC) is the most frequently diagnosed primary hepatic malignancy, which is currently the sixth most common cancer type and third leading cause of cancer-related death around the world [ 1 , 2 ]. Chronic hepatitis B and C virus (HBV, HCV) infections, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), as well as non-alcoholic steatohepatitis (NASH) are associated with HCC risk [ 3 , 4 , 5 ].…”