中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 12
Dec.  2021
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(12): 2943-2946

Research advances in systemic therapy for advanced hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2021.12.044

  • The Third Ward of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China

  • Received Date: 2021-05-25
  • Accepted Date: 2021-07-20
  • Published Date: 2021-12-20
    Abstract
  • Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis, and surgical resection is the preferred method for the treatment of HCC, but it has a limited therapeutic effect on advanced HCC, while systemic treatment plays an important role in the treatment of advanced unresectable HCC. This article summarizes the advances in systemic therapy for unresectable liver cancer in China and globally in recent years, including a variety of tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib, and cabozantinib) and immune checkpoint inhibitors (atezolizumab, pembrolizumab, and nivolumab). The analysis shows that for patients with unresectable HCC, systemic therapy can prolong the survival time of patients to a certain extent, and combined treatment regimen has become a new research hotspot. Individualized systemic treatment strategies will be further explored in the future.

     

    • FullText(HTML)
  • loading
    • References(36)
  • [1]
    BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. DOI: 10.3322/caac.21492.
    [2]
    SIEGEL RL, MILLER KD, JEMAL A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1): 7-30. DOI: 10.3322/caac.21590.
    [3]
    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. 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.
    [4]
    LLOVET JM, RICCI S, MAZZAFERRO V, et al. Sorafenib in advanced hepatocellular carcinoma[J]. N Engl J Med, 2008, 359(4): 378-390. DOI: 10.1056/NEJMoa0708857.
    [5]
    CHENG AL, KANG YK, CHEN Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: A phase Ⅲ randomised, double-blind, placebo-controlled trial[J]. Lancet Oncol, 2009, 10(1): 25-34. DOI: 10.1016/S1470-2045(08)70285-7.
    [6]
    BRUIX J, RAOUL JL, SHERMAN M, et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase Ⅲ trial[J]. J Hepatol, 2012, 57(4): 821-829. DOI: 10.1016/j.jhep.2012.06.014.
    [7]
    VOGEL A, SABOROWSKI A. Current strategies for the treatment of intermediate and advanced hepatocellular carcinoma[J]. Cancer Treat Rev, 2020, 82: 101946. DOI: 10.1016/j.ctrv.2019.101946.
    [8]
    BRUIX J, CHENG AL, MEINHARDT G, et al. Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase Ⅲ studies[J]. J Hepatol, 2017, 67(5): 999-1008. DOI: 10.1016/j.jhep.2017.06.026.
    [9]
    BERHANE S, FOX R, GARCÍA-FIÑANA M, et al. Using prognostic and predictive clinical features to make personalised survival prediction in advanced hepatocellular carcinoma patients undergoing sorafenib treatment[J]. Br J Cancer, 2019, 121(2): 117-124. DOI: 10.1038/s41416-019-0488-4.
    [10]
    KUDO M, FINN RS, QIN S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial[J]. Lancet, 2018, 391(10126): 1163-1173. DOI: 10.1016/S0140-6736(18)30207-1.
    [11]
    KUDO M, UESHIMA K, CHAN S, et al. Lenvatinib as an initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond Up-To-seven criteria and Child-Pugh a liver function: A proof-of-concept study[J]. Cancers (Basel), 2019, 11(8): 1084. DOI: 10.3390/cancers11081084.
    [12]
    SHO T, SUDA G, OGAWA K, et al. Lenvatinib in patients with unresectable hepatocellular carcinoma who do not meet the REFLECT trial eligibility criteria[J]. Hepatol Res, 2020, 50(8): 966-977. DOI: 10.1111/hepr.13511.
    [13]
    VOGEL A, FRENETTE C, SUNG MW, et al. Baseline liver function and outcomes in the phase Ⅲ REFLECT study in patients with unresectable hepatocellular carcinoma (uHCC)[J]. J Clin Oncol, 2020, 38(suppl 4): 524. DOI: 10.1200/JCO.2020.38.4_suppl.524.
    [14]
    HATANAKA T, KAKIZAKI S, NAGASHIMA T, et al. Analyses of objective response rate, progression-free survival, and adverse events in hepatocellular carcinoma patients treated with lenvatinib: A multicenter retrospective study[J]. Hepatol Res, 2020, 50(3): 382-395. DOI: 10.1111/hepr.13460.
    [15]
    MARUTA S, OGASAWARA S, OOKA Y, et al. Potential of lenvatinib for an expanded indication from the REFLECT trial in patients with advanced hepatocellular carcinoma[J]. Liver Cancer, 2020, 9(4): 382-396. DOI: 10.1159/000507022.
    [16]
    BI F, QIN S, GU S, et al. Donafenib versus sorafenib as first-line therapy in advanced hepatocellular carcinoma: An open-label, randomized, multicenter phase Ⅱ/Ⅲ trial[J]. J Clin Oncol, 2020, 38(15): 4506-4506. DOI: 10.1200/JCO.21.00163.
    [17]
    LEE MS, RYOO BY, HSU CH, et al. Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): An open-label, multicentre, phase 1b study[J]. Lancet Oncol, 2020, 21(6): 808-820. DOI: 10.1016/S1470-2045(20)30156-X.
    [18]
    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.
    [19]
    GALLE PR, FINN RS, QIN S, et al. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): An open-label, randomised, phase 3 trial[J]. Lancet Oncol, 2021, 22(7): 991-1001. DOI: 10.1016/S1470-2045(21)00151-0.
    [20]
    BRUIX J, QIN S, MERLE P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): A randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet, 2017, 389(10064): 56-66. DOI: 10.1016/S0140-6736(16)32453-9.
    [21]
    FINN RS, MERLE P, GRANITO A, et al. Outcomes of sequential treatment with sorafenib followed by regorafenib for HCC: Additional analyses from the phase Ⅲ RESORCE trial[J]. J Hepatol, 2018, 69(2): 353-358. DOI: 10.1016/j.jhep.2018.04.010.
    [22]
    ABOU-ALFA GK, MEYER T, CHENG AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma[J]. N Engl J Med, 2018, 379(1): 54-63. DOI: 10.1056/NEJMoa1717002.
    [23]
    KELLEY RK, RYOO BY, MERLE P, et al. Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: A subgroup analysis of the phase 3 CELESTIAL trial[J]. ESMO Open, 2020, 5(4). DOI: 10.1136/esmoopen-2020-000714.
    [24]
    RIMASSA L, WÖRNS MA. Navigating the new landscape of second-line treatment in advanced hepatocellular carcinoma[J]. Liver Int, 2020, 40(8): 1800-1811. DOI: 10.1111/liv.14533.
    [25]
    DEBAILLON VESQUE A, DECRAECKER M, BLANC JF. Profile of cabozantinib for the treatment of hepatocellular carcinoma: Patient selection and special considerations[J]. J Hepatocell Carcinoma, 2020, 7: 91-99. DOI: 10.2147/JHC.S195570.
    [26]
    KELLEY RK, W OLIVER J, HAZRA S, et al. Cabozantinib in combination with atezolizumab versus sorafenib in treatment-naive advanced hepatocellular carcinoma: COSMIC-312 Phase Ⅲ study design[J]. Future Oncol, 2020, 16(21): 1525-1536. DOI: 10.2217/fon-2020-0283.
    [27]
    ZHU AX, PARK JO, RYOO BY, et al. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): A randomised, double-blind, multicentre, phase 3 trial[J]. Lancet Oncol, 2015, 16(7): 859-870. DOI: 10.1016/S1470-2045(15)00050-9.
    [28]
    ZHU AX, KANG YK, YEN CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): A randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet Oncol, 2019, 20(2): 282-296. DOI: 10.1016/S1470-2045(18)30937-9.
    [29]
    KUZUYA T, ISHIGAMI M, ITO T, et al. Initial experience of ramucirumab treatment after lenvatinib failure for patients with advanced hepatocellular carcinoma[J]. Anticancer Res, 2020, 40(4): 2089-2093. DOI: 10.21873/anticanres.14167.
    [30]
    ZHU AX, NIPP RD, FINN RS, et al. Ramucirumab in the second-line for patients with hepatocellular carcinoma and elevated alpha-fetoprotein: Patient-reported outcomes across two randomised clinical trials[J]. ESMO Open, 2020, 5(4): e000797. DOI: 10.1136/esmoopen-2020-000797.
    [31]
    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.
    [32]
    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.
    [33]
    FINN RS, IKEDA M, ZHU AX, et al. Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma[J]. J Clin Oncol, 2020, 38(26): 2960-2970. DOI: 10.1200/JCO.20.00808.
    [34]
    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.
    [35]
    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. DOI: 10.1093/annonc/mdz394.029
    [36]
    YAU T, KANG YK, KIM TY, et al. Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: The checkmate 040 randomized clinical trial[J]. JAMA Oncol, 2020, 6(11): e204564. DOI: 10.1001/jamaoncol.2020.4564.
    • 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
    Get Citation
    PDF
    XML

    Article Metrics

    Article views (579) 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