中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 2
Mar.  2021
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(2): 437-443

Advances in the application of programmed death-1/programmed death-ligand 1 inhibitors in the treatment of hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2021.02.040
  • 1.

    Hepato-pancreato-biliary Center, Department of Hepatology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China

  • 2.

    Hepato-pancreato-biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China

  • Received Date: 2020-06-22
  • Accepted Date: 2020-09-18
  • Published Date: 2021-02-20
    Abstract
  • Hepatocellular carcinoma (HCC) is one of the most common malignancies in China, and due to the lack of specific symptoms, more than half of these patients are in the advanced stage at the time of initial diagnosis. Targeted therapy and systemic chemotherapies are the main treatment methods for advanced HCC with limited efficacy. In recent years, immunotherapy has been developed rapidly. This article introduces the current status of the immune checkpoint inhibitors, programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, in the treatment of HCC, summarizes the latest data of several clinical trials, and analyzes the safety and efficacy of monotherapy and combination therapy. The analysis shows that immunotherapy has become one of the important methods for systemic treatment, and combination therapy can significantly improve the outcome of HCC with a manageable safety profile, which is an important direction for future development.

     

    • FullText(HTML)
  • loading
    • References(34)
  • [1]
    Bureau of Medical Administration, National Health Commission of the People's Republic of China. Guidelines for diagnosis and treatment of primary liver cancer in China (2019 edition)[J]. J Clin Hepatol, 2020, 36(2): 277-292. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2020.02.007

    中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版)[J]. 临床肝胆病杂志, 2020, 36(2): 277-292. DOI: 10.3969/j.issn.1001-5256.2020.02.007
    [2]
    PARDOLL DM. The blockade of immune checkpoints in cancer immunotherapy[J]. Nat Rev Cancer, 2012, 12(4): 252-264. DOI: 10.1038/nrc3239
    [3]
    EL-KHOUEIRY AB, SANGRO B, YAU T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): An open-label, non-comparative, phase 1/2 dose escalation and expansion trial[J]. Lancet, 2017, 389(10088): 2492-2502. DOI: 10.1016/S0140-6736(17)31046-2
    [4]
    CROCENZI TS, EL-KHOUEIRY AB, YAU T, et al. Nivolumab in sorafenib-naive and-experienced patients with advanced hepatocellular carcinoma: CheckMate 040 study[J]. J Clin Oncol, 2017, 35(15 Suppl): 4013.
    [5]
    YAU T, HSU C, KIM TY, et al. Nivolumab in advanced hepatocellular carcinoma: Sorafenib-experienced Asian cohort analysis[J]. J Hepatol, 2019, 71(3): 543-552. DOI: 10.1016/j.jhep.2019.05.014
    [6]
    KUDO M, MATILLA A, SANTORO A, et al. Checkmate-040: Nivolumab (NIVO) in patients (pts) with advanced hepatocellular carcinoma (aHCC) and Child-Pugh B (CPB) status[J]. J Clin Oncol, 2019, 37(4 Suppl): 327.
    [7]
    KAMBHAMPATI S, BAUER KE, BRACCI PM, et al. Nivolumab in patients with advanced hepatocellular carcinoma and Child-Pugh class B cirrhosis: Safety and clinical outcomes in a retrospective case series[J]. Cancer, 2019, 125(18): 3234-3241. DOI: 10.1002/cncr.32206
    [8]
    YAU T, PARK JW, FINN RS, et al. CheckMate 459: A randomized, multi-center phase Ⅲ study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC)[J]. Ann Oncol, 2019, 30(Suppl 5): v874-v875.
    [9]
    SUN YK. Interpretation of CSCO guidelines for the diagnosis and treatment of primary liver cancer: Systemic treatment[J/CD]. Electronic J Liver Tumor, 2018, 5(3): 11-14. (in Chinese)

    孙永琨. 2018《CSCO原发性肝癌诊疗指南》解读——全身治疗部分[J/CD]. 肝癌电子杂志, 2018, 5(3): 11-14.
    [10]
    National Comprehensive Cancer Network(NCCN). Clinical Practice Guidelines in Oncology. Hepatobiliary Cancers, Version 1.2020.[EB/OL]. (2020-03-23)[2020-06-20]. https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf.
    [11]
    ZHU AX, FINN RS, EDELINE J, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): A non-randomised, open-label phase 2 trial[J]. Lancet Oncol, 2018, 19(7): 940-952. DOI: 10.1016/S1470-2045(18)30351-6
    [12]
    KUDO M, FINN RS, EDELINE J, et al. Updated efficacy and safety of KEYNOTE-224: A phase Ⅱ study of pembrolizumab (pembro) in patients with advanced hepatocellular carcinoma (HCC)[J]. J Clin Oncol, 2020, 38(4 Suppl): 518.
    [13]
    FINN RS, RYOO BY, MERLE P, et al. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: A randomized, double-blind, phase Ⅲ trial[J]. J Clin Oncol, 2020, 38(3): 193-202. DOI: 10.1200/JCO.19.01307
    [14]
    BENSON AB, D'ANGELICA MI, ABBOTT DE, et al. Guidelines insights: Hepatobiliary cancers, Version 2.2019[J]. J Natl Compr Canc Netw, 2019, 17(4): 302-310. DOI: 10.6004/jnccn.2019.0019
    [15]
    QIN S, REN Z, MENG Z, et al. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: A multicentre, open-label, parallel-group, randomised, phase 2 trial[J]. Lancet Oncol, 2020, 21(4): 571-580. DOI: 10.1016/S1470-2045(20)30011-5
    [16]
    WAINBERG ZA, SEGAL NH, JAEGER D, et al. Safety and clinical activity of durvalumab monotherapy in patients with hepatocellular carcinoma (HCC)[J]. J Clin Oncol, 2017, 35(15 Suppl): 4071.
    [17]
    FENG Z, RONG P, WANG W. Meta-analysis of the efficacy and safety of PD-1/PD-L1 inhibitors administered alone or in combination with anti-VEGF agents in advanced hepatocellular carcinoma[J]. Gut, 2020, 69(10): 1904-1906. DOI: 10.1136/gutjnl-2019-320116
    [18]
    KUDO M. Immuno-oncology therapy for hepatocellular carcinoma: Current status and ongoing trials[J]. Liver Cancer, 2019, 8(4): 221-238. DOI: 10.1159/000501501
    [19]
    ZHU AX, FINN RS, IKEDA M, et al. A phase Ib study of lenvatinib (LEN) plus pembrolizumab (PEMBRO) in unresectable hepatocellular carcinoma (uHCC)[J]. J Clin Oncol, 2020, 38(15 Suppl): 4519.
    [20]
    LLOVET JM, KUDO M, CHENG AL, et al. Lenvatinib (len) plus pembrolizumab (pembro) for the first-line treatment of patients (pts) with advanced hepatocellular carcinoma (HCC): Phase 3 LEAP-002 study[J]. J Clini Oncol, 2019, 37(15 Suppl): TPS4152.
    [21]
    KUDO M, IKEDA M, MOTOMURA K, et al. A phase Ib study of lenvatinib (LEN) plus nivolumab (NIV) in patients (pts) with unresectable hepatocellular carcinoma (uHCC): Study 117[J]. J Clin Oncol, 2020, 38(4 Suppl): 513.
    [22]
    XU J, ZHANG Y, JIA R, et al. Anti-PD-1 antibody SHR-1210 combined with apatinib for advanced hepatocellular carcinoma, gastric, or esophagogastric junction cancer: An open-label, dose escalation and expansion study[J]. Clin Cancer Res, 2019, 25(2): 515-523. DOI: 10.1158/1078-0432.CCR-18-2484
    [23]
    KUDO M, MOTOMURA K, WADA Y, et al. First-line avelumab + axitinib in patients with advanced hepatocellular carcinoma: Results from a phase 1b trial (VEGF Liver 100)[J]. J Clin Oncol, 2019, 37(15 Suppl): 4072.
    [24]
    RIMASSA L, CHENG AL, BRAITEH F, et al. Phase Ⅲ (COSMIC-312) study of cabozantinib (C) in combination with atezolizumab (A) vs sorafenib (S) in patients (pts) with advanced hepatocellular carcinoma (aHCC) who have not received previous systemic anticancer therapy[J]. Ann Oncol, 2019, 30(Suppl 5): v320.
    [25]
    LEE M, RYOO BY, HSU CH, et al. Randomised efficacy and safety results for atezolizumab (Atezo) + bevacizumab (Bev) in patients (pts) with previously untreated, unresectable hepatocellular carcinoma (HCC)[J]. Ann Oncol, 2019, 30(Suppl 5): v875.
    [26]
    FINN RS, QIN S, IKEDA M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma[J]. N Engl J Med, 2020, 382(20): 1894-1905. DOI: 10.1056/NEJMoa1915745
    [27]
    CHENG AL, QIN S, IKEDA M, et al. IMbrave150: Efficacy and safety results from a ph Ⅲ study evaluating atezolizumab (atezo)+bevacizumab (bev) vs sorafenib (Sor) as first treatment (tx) for patients (pts) with unresectable hepatocellular carcinoma (HCC)[J]. Ann Oncol, 2019, 30(Suppl 9): ix186-ix187.
    [28]
    QIN SK, REN ZG, FENG YS, et al. OP02-03 efficacy and safety of atezolizumab + bevacizumab vs sorafenib in Chinese patients with unresectable HCC in the phase Ⅲ IMbrave150 study.[EB/OL]. (2020-02-06)[2020-06-20]. https://easl.eu/livercancersummit2020/wp-content/uploads/2020/01/Liver-Cancer-Summit-2020-Abstract-book.pdf.
    [29]
    YAU T, KANG YK, KIM TY, et al. Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040[J]. J Clin Oncol, 2019, 37(15 Suppl): 4012.
    [30]
    HE AR, YAU T, HSU C, et al. Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Subgroup analyses from CheckMate 040[J]. J Clin Oncol, 2020, 38(4 Suppl): 512.
    [31]
    KELLEY RK, SANGRO B, HARRIS WP, et al. Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab (T) in combination with durvalumab (D) for patients (pts) with advanced hepatocellular carcinoma (aHCC)[J]. J Clin Oncol, 2020, 38(15 Suppl): 4508.
    [32]
    ABOU-ALFA GK, CHAN SL, FURUSE J, et al. A randomized, multicenter phase 3 study of durvalumab (D) and tremelimumab (T) as first-line treatment in patients with unresectable hepatocellular carcinoma (HCC): HIMALAYA study[J]. J Clin Oncol, 2018, 36(15 Suppl): TPS4144.
    [33]
    QIN S, CHEN Z, LIU Y, et al. A phase Ⅱ study of anti-PD-1 antibody camrelizumab plus FOLFOX4 or GEMOX systemic chemotherapy as first-line therapy for advanced hepatocellular carcinoma or biliary tract cancer[J]. J Clin Oncol, 2019, 37(15 Suppl): 4074.
    [34]
    YAU T, ZAGONEL V, SANTORO A, et al. Nivolumab (NIVO)+ipilimumab (IPI)+cabozantinib (CABO) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040[J]. J Clin Oncol, 2020, 38(4 Suppl): 478.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(1)  / Tables(2)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (541) PDF downloads(64) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return