Emerging role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma
Vito Longo1, Oronzo Brunetti2, Antonio Gnoni3
1Medical Thoracic Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II" of Bari, 70124 Bari, Italy. vito.longo79@tiscali.it.
Abstract:
Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70-80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib had been the standardcare for almost a decade until 2018 when the Food and Drug Administration approved an alternative first-line agent namely lenvatinib. Cabozantinib, regorafenib, and ramucirumab also displayed promising results in second line settings. FOLFOX4, however, results inan alternative first-line treatment for the Chineseclinical oncology guidelines. Moreover,nivolumab and pembrolizumab,two therapeutics against the Programmed death (PD)-ligand 1 (PD-L1)/PD1 axis have been recently approvedfor subsequent-line therapy. However, similar to other solid tumors, the response rate of single agent targeting PD-L1/PD1 axis is low. Therefore, a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors (ICIs), the addition of ICIs after resection or during loco-regional therapy, ICIs in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with a careful assessmentof new ICIs-based combinatory approaches.
Insights
Hepatocellular carcinoma (HCC) treatment is advancing with new immune checkpoint inhibitors (ICIs). Combinations of ICIs with other therapies show promise for improving outcomes in advanced liver cancer.
Area of Science:
- Hepatology
- Oncology
- Immunotherapy
Background:
- Hepatocellular carcinoma (HCC) is a leading cause of cancer death, with most patients diagnosed at advanced stages.
- Current treatments like lenvatinib and sorafenib have limitations, and novel therapeutic strategies are urgently needed.
- Immune checkpoint inhibitors (ICIs) targeting the PD-L1/PD1 axis offer new hope, but single-agent efficacy is often limited.
Purpose of the Study:
- To review the current landscape of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) treatment.
- To critically assess novel combination strategies involving ICIs for advanced HCC.
- To highlight emerging therapeutic approaches for improving HCC patient outcomes.
Main Methods:
- Literature review of clinical trials and research studies on ICIs in HCC.
- Analysis of data on single-agent and combination therapies, including ICIs with chemotherapy, targeted agents, and other immunotherapies.
- Evaluation of treatment outcomes, response rates, and safety profiles of various ICI-based approaches.
Main Results:
- Single-agent PD-L1/PD1 inhibitors show limited response rates in HCC.
- Combinatorial approaches, including ICIs with kinase inhibitors or anti-angiogenic agents, are under active investigation.
- ICIs are being explored in neoadjuvant, adjuvant, and loco-regional settings, alongside systemic therapies.
Conclusions:
- Immune checkpoint inhibitors represent a significant advancement in HCC therapy.
- Combinations of ICIs with other modalities are crucial for enhancing treatment efficacy and overcoming resistance.
- Further research into ICI-based strategies holds promise for improving survival in patients with advanced hepatocellular carcinoma.
More Related Videos
Related Concept Videos
01:27Tumor Immunotherapy
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...