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免疫疗法在肝细胞癌治疗中的作用:当前标准和未来方向。

Role of immunotherapy in the management of hepatocellular carcinoma: current standards and future directions.

机构信息

Department of Internal Medicine i, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.

出版信息

Curr Oncol. 2020 Nov;27(Suppl 3):S152-S164. doi: 10.3747/co.27.7315. Epub 2020 Nov 1.


DOI:10.3747/co.27.7315
PMID:33343209
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7739523/
Abstract

The multikinase inhibitor sorafenib was the only approved systemic therapy in advanced hepatocellular carcinoma (hcc) for about a decade. In recent years, the number of approved agents has increased significantly as a result of a number of positive phase iii clinical trials. Lenvatinib as a first-line treatment, and regorafenib, cabozantinib, and ramucirumab in the second-line setting are now approved by the U.S. Food and Drug Administration (fda) and the European Medicines Agency. In phase ii studies, immunotherapy with nivolumab and monotherapy using pembrolizumab yielded impressive results for overall survival in therapy-naïve and pretreated patients, leading to the accelerated approval by the fda of nivolumab and pembrolizumab for second-line treatment. However, phase iii trials of nivolumab in the first line and pembrolizumab in the second line as single agents failed to reach statistical significance, although clinical benefit for a subset of patients with long durations of response could be demonstrated. Despite that setback, immunotherapy for hcc is a promising therapeutic approach, and the combination of immunotherapy with other treatment modalities such as monoclonal antibodies, tyrosine kinase inhibitors, or local therapies has the potential to increase the overall response rate and survival. Recently, the results of a phase iii trial of combination atezolizumab-bevacizumab compared with sorafenib showed a highly significant survival benefit and median overall survival that was not reached in the immunotherapy arm, making the combination the preferred standard of care in first-line therapy. Despite the impressive results and generally good toxicity profile of immunotherapy, patients who respond to therapy constitute only a subset of the overall population, and response rates are still limited. This review focuses on the currently reported results and ongoing clinical trials of checkpoint inhibitor-based immunotherapy in hcc.

摘要

多激酶抑制剂索拉非尼是近十年来晚期肝细胞癌 (hcc) 唯一被批准的系统治疗药物。近年来,由于多项阳性三期临床试验的结果,被批准的药物数量显著增加。仑伐替尼作为一线治疗药物,regorafenib、cabozantinib 和 ramucirumab 作为二线治疗药物,现已获得美国食品和药物管理局 (fda) 和欧洲药品管理局 (ema) 的批准。在二期研究中,nivolumab 免疫治疗和 pembrolizumab 单药治疗在未经治疗和预处理的患者中均取得了令人瞩目的总生存期结果,促使 fda 加速批准 nivolumab 和 pembrolizumab 用于二线治疗。然而,nivolumab 一线和 pembrolizumab 二线作为单药的三期试验未能达到统计学意义,尽管可以证明对一部分患者的临床获益具有较长的反应持续时间。尽管存在这一挫折,但 HCC 的免疫治疗是一种很有前途的治疗方法,免疫治疗与其他治疗方式(如单克隆抗体、酪氨酸激酶抑制剂或局部治疗)的联合有可能提高总体反应率和生存率。最近,atezolizumab-bevacizumab 联合治疗与索拉非尼比较的三期试验结果显示,免疫治疗组具有显著的生存获益和未达到的中位总生存期,使该联合治疗成为一线治疗的首选标准。尽管免疫治疗具有令人印象深刻的结果和良好的总体毒性特征,但对治疗有反应的患者仅占总体人群的一部分,并且反应率仍然有限。这篇综述重点介绍了 HCC 基于检查点抑制剂的免疫治疗的目前报道结果和正在进行的临床试验。

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引用本文的文献

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Effect of regorafenib combined with immunotherapy and arterial chemoembolization on the survival of patients with advanced hepatocellular carcinoma: a retrospective study.

Am J Transl Res. 2025-3-15

[2]
Economic evaluation of camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma in the United States and China.

Int J Clin Pharm. 2024-10

[3]
Hepatocellular Carcinoma from a Hepatologist's Perspective.

Semin Intervent Radiol. 2024-1-24

[4]
Synergistic Effects of Nanoscale CaO Combined with PD-1 Inhibitors in the Treatment of Hepatocellular Carcinoma: A Promising Combination.

Int J Nanomedicine. 2024

[5]
Real-world treatment patterns, clinical outcomes, and health care resource utilization in advanced unresectable hepatocellular carcinoma.

Can Liver J. 2022-11-7

[6]
Immune checkpoint inhibitor therapy for hepatocellular carcinoma.

Ann Gastroenterol. 2022

[7]
Perspectives of traditional Chinese medicine to patch up immune checkpoint blockers.

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[8]
Comprehensive Review of Hepatocellular Carcinoma in India: Current Challenges and Future Directions.

JCO Glob Oncol. 2022-10

[9]
Pretreatment Modified Albumin-Bilirubin Grade Is an Important Predictive Factor Associated with the Therapeutic Response and the Continuation of Atezolizumab plus Bevacizumab Combination Therapy for Patients with Unresectable Hepatocellular Carcinoma.

Curr Oncol. 2022-7-8

[10]
Diagnostic Value, Prognostic Value, and Immune Infiltration of Family Members in Liver Cancer: Bioinformatic Analysis.

Front Oncol. 2022-3-4

本文引用的文献

[1]
Avelumab in Combination with Axitinib as First-Line Treatment in Patients with Advanced Hepatocellular Carcinoma: Results from the Phase 1b VEGF Liver 100 Trial.

Liver Cancer. 2021-6

[2]
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J Clin Transl Hepatol. 2020-6-28

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J Immunother Cancer. 2020-6

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N Engl J Med. 2020-5-14

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Lancet Oncol. 2020-2-26

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Effects of Subsequent Systemic Anticancer Medication Following First-Line Lenvatinib: A Post Hoc Responder Analysis from the Phase 3 REFLECT Study in Unresectable Hepatocellular Carcinoma.

Liver Cancer. 2020-1

[10]
Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial.

J Clin Oncol. 2019-12-2

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