ABSTRACT
Introduction
Hepatocellular carcinoma (HCC) represents the sixth most commonly diagnosed malignancy worldwide, accounting for millions of deaths annually. Despite immune checkpoint inhibitors (ICIs) reported important results, only a minority of HCC patients benefit from these treatments, and the identification of predictive biomarkers of response still remains a highly unmet need.
Areas covered
Herein, we provide a timely overview of available evidence on biochemical predictors of response to immunotherapy in advanced HCC patients; we speculate on how PD-L1, TMB, and other emerging biomarkers could assist drug clinical trials in the near future. A literature search was conducted in June 2021 using Pubmed/Medline, Cochrane library, and Scopus databases.
Expert opinion
Reliable predictors of response to ICIs are of pivotal importance to allow a proper stratification and selection of HCC patients that could derive more benefit from immunotherapy. Well-designed, multicenter clinical trials specifically focused on predictive biomarkers are warranted in this setting, where most of evidence currently derives from retrospective, single-center studies with small sample size.
Article Highlights
Despite the evolution and emergence of novel treatment options, the overall survival of patients with advanced hepatocellular carcinoma (HCC) is poor.
The identification of predictive biomarkers [which can guide disease-monitoring and treatment decision-making in HCC patients receiving immunotherapy] is crucial for progress of pharmacological treatment success.
The predictive value of tumor mutational burden (TMB) has not been prospectively validated.
No single biomarker has the predictive value for stratifying and to selecting HCC patients that are more likely to respond to immune checkpoint inhibitors [ICIs].
Well-designed, large-cohort, multicenter clinical trials specifically focused on predictors of response to immunotherapy in HCC patients are necessary which could eventually assist clinicians in the clinical decision-making processes for immunotherapy HCC patients.
The HCC medical research community should further efforts to identify predictive biomarkers.
Reviewer disclosures
Peer reviewers in this manuscript have no relevant financial or other relationships to disclose
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.