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Real-World Use of Immunotherapy for Hepatocellular Carcinoma

Overview
Journal Pragmat Obs Res
Publisher Dove Medical Press
Specialty General Medicine
Date 2023 Aug 28
PMID 37637511
Authors
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Abstract

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide and accounts for 90% of all primary liver cancers. Chronic inflammation is the hallmark across most prevalent etiologies among which HBV is the leading cause worldwide (33%), followed by alcohol (30%), HCV (21%), other factors like non-alcoholic steatohepatitis linked to insulin resistance/metabolic syndrome, and obesity associated inflammation (16%). Deregulation of the tightly controlled immunological network leads to liver disease, including chronic infection, autoimmunity, and tumor development. While inflammation drives oncogenesis in the liver, HCC also recruits ICOS+ FOXP3+ Tregs and MDSCs and upregulates immune checkpoints to induce a state of immunosuppression in the tumor microenvironment. As such, research is focused on targeting and modulating the immune system to treat HCC. The Checkmate 040 and Keynote 224 studies established the role of immunotherapy in the treatment of patients with HCC. In Phase I and II trials, nivolumab and pembrolizumab demonstrated durable response rates of 15-20% and were subsequently approved as second-line agents after sorafenib. Due to the success of the IMbrave 150 and HIMALAYA trials, which examined the combination of atezolizumab/bevacizumab and tremelimumab/durvalumab, respectively, the FDA approved these regimens as first-time treatment options for patients with advanced HCC. The encouraging results of immunotherapy in the management of HCC has led researchers to evaluate if combination with locoregional therapies may result in a synergistic effect. Real-world studies represent an invaluable tool to assess and verify the applicability of clinical trials in the bedside setting with a more varied patient population. We herein review current real-life use of ICIs in the management of HCC and highlight some of the ongoing clinical trials that are expected to change current recommended first-line treatment in the near future.

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References
1.
Llovet J, De Baere T, Kulik L, Haber P, Greten T, Meyer T . Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2021; 18(5):293-313. DOI: 10.1038/s41575-020-00395-0. View

2.
Bratman S, Yang S, Iafolla M, Liu Z, Hansen A, Bedard P . Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nat Cancer. 2022; 1(9):873-881. DOI: 10.1038/s43018-020-0096-5. View

3.
Harding J, Nandakumar S, Armenia J, Khalil D, Albano M, Ly M . Prospective Genotyping of Hepatocellular Carcinoma: Clinical Implications of Next-Generation Sequencing for Matching Patients to Targeted and Immune Therapies. Clin Cancer Res. 2018; 25(7):2116-2126. PMC: 6689131. DOI: 10.1158/1078-0432.CCR-18-2293. View

4.
Chen Y, Chen Y, Wang J, Hung C . Efficacy and Safety of Lenvatinib After Progression on First-line Atezolizumab Plus Bevacizumab Treatment in Advanced Hepatocellular Carcinoma Patients. Anticancer Res. 2023; 43(3):1377-1384. DOI: 10.21873/anticanres.16286. View

5.
Goldman J, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D . Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2020; 22(1):51-65. DOI: 10.1016/S1470-2045(20)30539-8. View