Immune Checkpoint Inhibition in Hepatocellular Carcinoma: Basics and Ongoing Clinical Trials
1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
Abstract:
Clinical trials of antibodies targeting the immune checkpoint inhibitors programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) for the treatment of advanced hepatocellular carcinoma (HCC) are ongoing. Expansion cohorts of a phase I/II trial of the anti-PD-1 antibody nivolumab in advanced HCC showed favorable results. Two phase III studies are currently ongoing: a comparison of nivolumab and sorafenib in the first-line setting for advanced HCC, and a comparison of the anti-PD-1 antibody pembrolizumab and a placebo in the second-line setting for patients with advanced HCC who progressed on sorafenib therapy. The combination of anti-PD-1/PD-L1 and anti-CTLA-4 antibodies is being evaluated in other phase I/II trials, and the results suggest that an anti-PD-1 antibody combined with locoregional therapy or other molecular targeted agents is an effective treatment strategy for HCC. Immune checkpoint inhibitors may therefore open new doors to the treatment of HCC.
Insights
Immune checkpoint inhibitors like PD-1 and CTLA-4 antibodies show promise for advanced hepatocellular carcinoma (HCC). Ongoing trials evaluate these agents alone and in combination, suggesting new treatment avenues for HCC.
Area of Science:
- Oncology
- Immunology
- Hepatology
Background:
- Advanced hepatocellular carcinoma (HCC) remains a challenging malignancy with limited treatment options.
- Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have emerged as a promising therapeutic strategy.
Purpose of the Study:
- To review the current clinical trial landscape of ICIs in advanced HCC.
- To highlight the potential of ICIs as a novel treatment modality for HCC.
Main Methods:
- Review of ongoing and recently completed clinical trials involving ICIs in advanced HCC.
- Analysis of preliminary results from phase I/II and phase III studies.
Main Results:
- Favorable results have been observed with nivolumab (anti-PD-1) in expansion cohorts of a phase I/II trial for advanced HCC.
- Two phase III studies are underway comparing nivolumab to sorafenib in the first-line setting and pembrolizumab (anti-PD-1) to placebo in the second-line setting.
- Combination therapies involving anti-PD-1/PD-L1 and anti-CTLA-4 antibodies, as well as combinations with locoregional therapy or targeted agents, are under investigation and show efficacy.
Conclusions:
- Immune checkpoint inhibitors represent a significant advancement in the treatment of advanced HCC.
- Combination strategies and novel ICI agents hold promise for improving outcomes in HCC patients.
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