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Advances in Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is usually diagnosed in an advanced stage and has become the second deadliest type of cancer worldwide. The systemic treatment of advanced HCC has been a challenge, and for decades was limited to treatment with tyrosine kinase inhibitors (TKIs) until the application of immune checkpoint inhibitors (ICIs) became available. Due to drug resistance and unsatisfactory therapeutic effects of monotherapy with TKIs or ICIs, multi-ICIs, or the combination of ICIs with antiangiogenic drugs has become a novel strategy to treat advanced HCC. Antiangiogenic drugs mostly include TKIs (sorafenib, lenvatinib, regorafenib, cabozantinib and so on) and anti-vascular endothelial growth factor (VEGF), such as bevacizumab. Common ICIs include anti-programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1), including nivolumab, pembrolizumab, durvalumab, and atezolizumab, and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), including tremelimumab and ipilimumab. Combination therapies involving antiangiogenic drugs and ICIs or two ICIs may have a synergistic action and have shown greater efficacy in advanced HCC. In this review, we present an overview of the current knowledge and recent clinical developments in ICI-based combination therapies for advanced HCC and we provide an outlook on future prospects.

SUBMITTER: Chen Y

PROVIDER: S-EPMC9226303 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Advances in Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma.

Chen Yue Y Hu Haoyue H Yuan Xianglei X Fan Xue X Zhang Chengda C

Frontiers in immunology 20220610

Hepatocellular carcinoma (HCC) is usually diagnosed in an advanced stage and has become the second deadliest type of cancer worldwide. The systemic treatment of advanced HCC has been a challenge, and for decades was limited to treatment with tyrosine kinase inhibitors (TKIs) until the application of immune checkpoint inhibitors (ICIs) became available. Due to drug resistance and unsatisfactory therapeutic effects of monotherapy with TKIs or ICIs, multi-ICIs, or the combination of ICIs with antia ...[more]

PMID: 35757756

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Project description:Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. A first-line standard of care, sorafenib results in median overall survival of 12 months in patients with Child-Pugh class A disease and 6 months in patients with Child-Pugh class B disease with objective response rates (ORRs) not exceeding 19%. These low efficacy rates have driven research on alternative therapeutic options, particularly immune-checkpoint inhibitors (ICIs). We reviewed the response rates (estimated by RECIST 1.1 criteria) across patients with advanced HCC treated with ICIs in phase I-IV clinical trials published between December 2012 to December 2020; 17 reports were identified as eligible and included in the quantitative analysis. Within the selected studies, pembrolizumab + lenvatinib reached the highest absolute ORR (36%), with first-line atezolizumab + bevacizumab showing the second highest ORR (27.3%). With regard to second-line therapy, nivolumab + ipilimumab reached an ORR of 32%, and pembrolizumab alone resulted in an ORR of 17% among sorafenib-experienced patients with advanced HCC. In summary, current studies show high response rates of ICIs in patients with advanced HCC. Nonetheless, further studies are required in the second-line setting to further evaluate ICI therapeutic superiority. Finally, it is of particular interest to examine the therapeutic potential of ICIs for patients with decompensated liver disease (Child-Pugh class C), currently not eligible for any systemic therapy. IMPLICATIONS FOR PRACTICE: Immune-checkpoint inhibitors (ICIs) can provide high objective response rates (ORR, estimated with RECIST 1.1. criteria) when used as first-line treatment in advanced hepatocellular carcinoma, particularly pembrolizumab + lenvatinib (ORR 36%) or atezolizumab + bevacizumab (ORR 27.3%). In sorafenib-experienced patients, nivolumab + ipilimumab (ORR 32%) provided the highest ORR among ICI-based regimens. These findings emphasize high therapeutic potential of ICI-based therapies in patients with advanced hepatocellular carcinoma, although further studies are required to further validate and define their role in this context.

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Advances in Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma.

Publications

Advances in Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma.

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