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Published on: September 12, 2019
Real-World Use of Immunotherapy for Hepatocellular Carcinoma
Amir Sara1, Samantha M Ruff2, Anne M Noonan1
1Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Insights
Hepatocellular carcinoma (HCC) treatment is evolving with immunotherapy. Real-world data and ongoing trials explore combining immune checkpoint inhibitors (ICIs) with other therapies for advanced liver cancer.
Area of Science:
- Hepatology
- Medical Oncology
- Immunology
Background:
- Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally, often driven by chronic inflammation from viral hepatitis, alcohol, and metabolic syndrome.
- The tumor microenvironment in HCC promotes immunosuppression by recruiting regulatory cells and upregulating immune checkpoints.
- Modulating the immune system offers a promising therapeutic strategy for HCC.
Purpose of the Study:
- To review the current real-world application of immune checkpoint inhibitors (ICIs) in managing HCC.
- To highlight ongoing clinical trials investigating novel ICI combinations for HCC treatment.
- To assess the impact of immunotherapy on HCC management and future treatment paradigms.
Main Methods:
- Review of clinical trial data (Checkmate 040, Keynote 224, IMbrave 150, HIMALAYA) on immunotherapy efficacy in HCC.
- Analysis of real-world studies evaluating ICI use in diverse HCC patient populations.
- Identification and summary of ongoing clinical trials exploring ICI combinations with locoregional therapies.
Main Results:
- Immunotherapy agents like nivolumab and pembrolizumab showed durable responses in HCC, leading to their approval as second-line treatments.
- Combination regimens (atezolizumab/bevacizumab, tremelimumab/durvalumab) are now FDA-approved first-line options for advanced HCC.
- Real-world data are crucial for validating clinical trial findings in broader patient groups.
Conclusions:
- Immunotherapy has significantly advanced HCC treatment, offering new therapeutic options.
- Combination strategies, including immunotherapy with locoregional therapies, are under investigation for synergistic effects.
- Future research and real-world evidence will continue to shape the recommended first-line treatment for advanced HCC.
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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