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7 "Immune checkpoint inhibitors"
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Review Articles
Complications of immunotherapy in advanced hepatocellular carcinoma
Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
Received October 16, 2023  Accepted November 21, 2023  Published online November 29, 2023  
DOI: https://doi.org/10.17998/jlc.2023.11.21    [Accepted]
  • 391 Views
  • 28 Downloads
AbstractAbstract PDF
Immune checkpoint inhibitors (ICIs) are highly effective in cancer treatment; however, the risks associated with the treatment must be carefully balanced against the therapeutic benefits. Immune-related adverse events (irAEs) are generally unpredictable and may persist over an extended period. In this review, we analyzed common irAEs reported in highly cited original articles and systematic reviews. The prevalent adverse reactions include fatigue, pyrexia, rash, pruritus, diarrhea, decreased appetite, nausea, abdominal pain, constipation, hepatitis, and hypothyroidism. Therefore, it is crucial to conduct evaluations not only of gastrointestinal organs but also of cardiac, neurologic, endocrine (including the frequently affected thyroid), and ophthalmic systems before commencing ICIs. This review further explores commonly reported types of irAEs, specific irAEs associated with each ICI agent, rare yet potentially fatal irAEs, and available treatment options for managing them.
A multidisciplinary approach with immunotherapies for advanced hepatocellular carcinoma
Yu Rim Lee
J Liver Cancer. 2023;23(2):316-329.   Published online September 22, 2023
DOI: https://doi.org/10.17998/jlc.2023.09.04
  • 1,169 Views
  • 93 Downloads
  • 1 Citation
AbstractAbstract PDF
Hepatocellular carcinoma (HCC) is a highly aggressive disease that is usually diagnosed at an advanced stage. Advanced HCC has limited treatment options and often has a poor prognosis. For the past decade, tyrosine kinase inhibitors have been the only treatments approved for advanced HCC that have shown overall survival (OS) benefits; however, but their clinical efficacy has been limited. Recent trials have demonstrated promising advancements in survival outcomes through immunotherapy-based treatments, such as combinations of immune checkpoint inhibitors (ICIs) with other ICIs, antiangiogenic drugs, and locoregional therapies. The atezolizumab-bevacizumab and durvalumab-tremelimumab (STRIDE) regimen has significantly improved survival rates as a first-line treatment and has become the new standard of care. Therefore, combined treatments for advanced HCC can result in better treatment outcomes owing to their synergistic effects, which requires a multidisciplinary approach. Ongoing studies are examining other therapeutic innovations that can improve disease control and OS rates. Despite improvements in the treatment of advanced HCC, further studies on the optimal treatment selection and sequences, biomarker identification, combination approaches with other therapies, and development of novel immunotherapy agents are required. This review presents the current treatment options and clinical data of the ICI-based combination immunotherapies for advanced HCC from a multidisciplinary perspective.

Citations

Citations to this article as recorded by  
  • Reduced-Dose or Discontinuation of Bevacizumab Might Be Considered after Variceal Bleeding in Patients with Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab: Case Reports
    Kyeong-Min Yeom, Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
    Medicina.2024; 60(1): 157.     CrossRef
The role of lenvatinib in the era of immunotherapy of hepatocellular carcinoma
Matthew Man Pok Lee, Landon Long Chan, Stephen Lam Chan
J Liver Cancer. 2023;23(2):262-271.   Published online August 17, 2023
DOI: https://doi.org/10.17998/jlc.2023.07.17
  • 2,051 Views
  • 221 Downloads
  • 2 Citations
AbstractAbstract PDF
Hepatocellular carcinoma (HCC) frequently presents as advanced stage with poor prognosis and high mortality. Systemic treatment is the treatment of choice for advanced disease. In 2007, the first multi-kinase inhibitor (MKI) sorafenib was approved and shown to modestly prolong overall survival (OS). The progress of systemic therapy has been slow afterwards until 2018 when lenvatinib, another MKI, was shown to be non-inferior to sorafenib on median OS as the first-line therapy for HCC. Since then, remarkable progress has been achieved on the treatment of advanced HCC, including the development of second-line targeted treatment, including regorafenib, cabozantinib and ramucirumab from 2017 to 2019. A growing focus has been placed on immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte-associated protein 4. These ICIs have proven their potency in treating HCC as both initial and subsequent line of therapy. At present, both regimens of atezolizumab combined with bevacizumab, as well as the combination of tremelimumab and durvalumab, are recommended as the first-line treatments based on positive phase III clinical trials. With the advancement of ICIs, it is anticipated that the role of MKIs in the treatment of HCC will evolve. In this article, lenvatinib, one of the most commonly used MKIs in HCC, is chosen to be reviewed.

Citations

Citations to this article as recorded by  
  • Reduced-Dose or Discontinuation of Bevacizumab Might Be Considered after Variceal Bleeding in Patients with Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab: Case Reports
    Kyeong-Min Yeom, Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
    Medicina.2024; 60(1): 157.     CrossRef
  • The Position of Multikinase Inhibitors in the Era of Immune-Checkpoint Inhibitors for Hepatocellular Carcinoma
    Beom Kyung Kim
    Gut and Liver.2024; 18(1): 3.     CrossRef
Case Report
Concurrent transarterial radioembolization and combination atezolizumab/ bevacizumab treatment of infiltrative hepatocellular carcinoma with portal vein tumor thrombosis: a case report
Min Kyung Park, Su Jong Yu
J Liver Cancer. 2022;22(1):69-74.   Published online March 21, 2022
DOI: https://doi.org/10.17998/jlc.2022.03.09
  • 3,065 Views
  • 103 Downloads
  • 3 Citations
AbstractAbstract PDF
Treatment options for advanced hepatocellular carcinoma (HCC) have been rapidly evolving. Herein, we describe a patient with advanced HCC and portal vein tumor thrombosis (PVTT) who responded decisively to a multidisciplinary approach. The patient had an ill-defined infiltrative HCC (diffuse subtype), with several intrahepatic metastasis and tumor invasion of left portal vein. Concurrent use of transarterial radioembolization (TARE) and systemic therapeutics (atezolizumab + bevacizumab) ultimately proved successful. There was marked reduction in tumor volume after TARE and an additional three cycles of atezolizumab plus bevacizumab. This concurrent treatment was well tolerated, without adverse events during immunotherapy. The impressive results achieved suggest that concurrent TARE and combination atezolizumab/bevacizumab is a promising treatment approach for advanced HCC with PVTT.

Citations

Citations to this article as recorded by  
  • Combining immunotherapy with transarterial radioembolization
    ZeynepCeren Balaban Genc, Efe Soydemır, SevalAy Ersoy, Tunc Ones
    Indian Journal of Nuclear Medicine.2023; 38(2): 145.     CrossRef
  • The New Era of Systemic Treatment for Hepatocellular Carcinoma: From the First Line to the Optimal Sequence
    Maria Cerreto, Ferdinando Cardone, Lucia Cerrito, Leonardo Stella, Francesco Santopaolo, Maria Pallozzi, Antonio Gasbarrini, Francesca Romana Ponziani
    Current Oncology.2023; 30(10): 8774.     CrossRef
  • Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus?
    Won Hyeok Choe
    Journal of Liver Cancer.2022; 22(1): 1.     CrossRef
Review Articles
Advances in immune checkpoint inhibitors for hepatocellular carcinoma
Ji Won Han, Su-Hyung Park
J Liver Cancer. 2021;21(2):139-145.   Published online September 30, 2021
DOI: https://doi.org/10.17998/jlc.2021.09.24
  • 3,354 Views
  • 98 Downloads
  • 3 Citations
AbstractAbstract PDF
Hepatocellular carcinoma (HCC) is the fifth most common cancer, and the second leading cause of cancer-related death worldwide. Although recent advances in immune checkpoint inhibitor-based immunotherapy have initiated a new era for advanced HCC treatment, the majority of HCC patients receiving immune checkpoint blockades do not derive clinical benefit. Thus, there remains an urgent need for novel immunotherapeutic strategies with improved therapeutic efficacy. Here we review recent studies of immune checkpoint blockade in HCC, providing the necessary basis for the rational design of immunotherapy.

Citations

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  • Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies
    Logan Muzyka, Nicolas K. Goff, Nikita Choudhary, Michael T. Koltz
    International Journal of Molecular Sciences.2023; 24(13): 10456.     CrossRef
  • Integrative analysis of lactylation-related genes and establishment of a novel prognostic signature for hepatocellular carcinoma
    Diankui Cai, Xiaoqing Yuan, D. Q. Cai, Ang Li, Sijia Yang, Weibang Yang, Jinxin Duan, Wenfeng Zhuo, Jun Min, Li Peng, Jinxing Wei
    Journal of Cancer Research and Clinical Oncology.2023; 149(13): 11517.     CrossRef
  • Editorial on immune checkpoint inhibitors in the treatment of hepatocellular carcinoma
    Samantha M Ruff, Timothy M Pawlik
    Immunotherapy.2023; 15(16): 1323.     CrossRef
Systemic therapy for advanced hepatocellular carcinoma: consideration for selecting second-line treatment
Bo Hyun Kim, Joong-Won Park
J Liver Cancer. 2021;21(2):124-138.   Published online September 30, 2021
DOI: https://doi.org/10.17998/jlc.2021.09.23
  • 3,732 Views
  • 112 Downloads
  • 2 Citations
AbstractAbstract PDF
Several molecular-targeted agents have been tested as first- or second-line therapies for hepatocellular carcinoma (HCC) but failed to improve clinical outcomes; sorafenib has been the only approved systemic agent for treating HCC for almost 10 years. Regorafenib resulted in a significant improvement in overall survival and thus was approved for HCC patients previously treated with sorafenib. Subsequently, cabozantinib and ramucirumab demonstrated superior overall survival compared with placebos in phase III clinical trials. Immune checkpoint inhibitors such as nivolumab with or without ipilimumab and pembrolizumab are also available in some countries for patients who are unresponsive to sorafenib. Some second-line agents are available for patients who are unresponsive to sorafenib; however, little is known about the considerations for selecting appropriate secondline systemic agents. Hence, this study aimed to review the current and future perspectives of second-line systemic agents.

Citations

Citations to this article as recorded by  
  • Expression of Peptidyl Arginine Deiminase 2 Is Closely Associated with Recurrence in Patients with Hepatocellular Carcinoma
    Sunho Uhm, Yoon Ah Cho, Ji-Young Choe, Ji Won Park, Min-Jeong Kim, Won-Ho Han, Junyong Lee, Jung Woo Lee, Dong Woo Shin, Jae Seung Soh, Hyun Lim, Ho Suk Kang, Sung-Hoon Moon, Sung-Eun Kim
    Diagnostics.2023; 13(4): 659.     CrossRef
  • Expert consensus on the management of adverse events in patients receiving lenvatinib for hepatocellular carcinoma
    Bo Hyun Kim, Su Jong Yu, Wonseok Kang, Sung Bum Cho, Soo Young Park, Seung Up Kim, Do Young Kim
    Journal of Gastroenterology and Hepatology.2022; 37(3): 428.     CrossRef
Deciphering and Reversing Immunosuppressive Cells in the Treatment of Hepatocellular Carcinoma
Su Jong Yu, Tim F. Greten
J Liver Cancer. 2020;20(1):1-16.   Published online March 31, 2020
DOI: https://doi.org/10.17998/jlc.20.1.1
  • 6,441 Views
  • 190 Downloads
  • 3 Citations
AbstractAbstract PDF
Use of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) has been partially successful. However, most HCC patients do not respond to immunotherapy. HCC has been shown to induce several immune suppressor mechanisms in patients. These suppressor mechanisms include involvement of myeloid-derived suppressor cells, regulatory T-cells, functionally impaired dendritic cells (DCs), neutrophils, monocytes, and tumor associated macrophages. The accumulation of immunosuppressive cells may lead to an immunosuppressive tumor microenvironment as well as the dense fibrotic stroma which may contribute to immune tolerance. Our laboratory has been investigating different cellular mechanisms of immune suppression in HCC patients. In vitro as well as in vivo studies have demonstrated that abrogation of the suppressor cells enhances or unmasks tumor-specific antitumor immune responses. Two or three effective systemic therapies including ICIs and/or molecular targeted therapies and the addition of innovative combination therapies targeting immune suppressor cells may lead to increased immune recognition with a greater tumor response. We reviewed the literature for the latest research on immune suppressor cells in HCC, and here we provide a comprehensive summary of the recent studies in this field.

Citations

Citations to this article as recorded by  
  • Higher Number of Tumor-Infiltrating PD-L1+ Cells Is Related to Better Response to Multikinase Inhibitors in Hepatocellular Carcinoma
    Ji Won Han, Ji Hoon Kim, Dong Hyun Kim, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Jaegyoon Ahn, Hyun Yang, Pil Soo Sung
    Diagnostics.2023; 13(8): 1453.     CrossRef
  • Immune checkpoint inhibitors in HCC: Cellular, molecular and systemic data
    Uasim Harkus, Miriam Wankell, Pranavan Palamuthusingam, Craig McFarlane, Lionel Hebbard
    Seminars in Cancer Biology.2022; 86: 799.     CrossRef
  • Crosstalk between tumor-associated macrophages and neighboring cells in hepatocellular carcinoma
    Pil Soo Sung
    Clinical and Molecular Hepatology.2022; 28(3): 333.     CrossRef

JLC : Journal of Liver Cancer