中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 40 Issue 3
Mar.  2024
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2024  >  40(3): 539-549

Efficacy and safety of cryoablation combined with lenvatinib and anti-PD-1 monoclonal antibody in treatment of unresectable hepatocellular carcinoma

DOI: 10.12449/JCH240317

  • Division of Liver Diseases，The Fifth Medical Center of Chinese PLA General Hospital，Beijing 100039，China

Research funding:

National Science and Technology Major Project during the 13th Five-Year Plan Period (2018ZX10725506);

Beijing Natural Science Foundation (7212101)

More Information
  • Corresponding author: YANG Yongping， yongpingyang@hotmail.com （ORCID： 0000-0002-8307-1095）
  • Received Date: 2023-10-24
  • Accepted Date: 2023-11-22
  • Published Date: 2024-03-20
    Abstract
  •   Objective  To investigate whether anti-PD-1 monoclonal antibody can improve the efficacy and safety of cryoablation combined with lenvatinib in the treatment of unresectable hepatocellular carcinoma （HCC）.  Methods  A retrospective analysis was performed for 232 patients with unresectable HCC who were treated at The Fifth Medical Center of Chinese PLA General Hospital from January 2018 to December 2022， among whom 128 received cryoablation combined with lenvatinib （double combination） and 104 received cryoablation combined with lenvatinib and anti-PD-1 monoclonal antibody （triple combination）. Propensity score matching was performed at a ratio of 1∶1， and finally there were 86 patients in each group. The two groups were evaluated in terms of objective response rate （ORR）， disease control rate （DCR）， overall survival （OS）， progression-free survival （PFS）， and adverse events （AEs）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Survival curves were plotted， and the Kaplan-Meier method was used to calculate the survival rate of patients in both groups， while the log-rank test was used for comparison between the two groups. The Cox regression model was used to calculate hazard ratio （HR） and 95% confidence interval （CI） and perform the univariate and multivariate analyses of influencing factors for prognosis.  Results  The median follow-up time was 28 months， and there were 33 deaths （38.0%） in the triple combination group and 40 deaths （46.0%） in the double combination group. Compared with the double combination group， the triple combination group had significantly higher ORR （35.6% vs 14.5%， P=0.008） and DCR （86.1% vs 64.1%， P=0.003）. OS and PFS in the triple combination group were significantly higher than those in the double combination group （P=0.045 and 0.026）. The univariate and multivariate Cox proportional-hazards regression model analyses showed that treatment regimen （HR=0.60， P=0.038） and alpha-fetoprotein level （HR=2.37， P=0.001） were independent risk factors for OS， and treatment regimen （HR=0.65， P=0.025）， diabetes mellitus （HR=1.94， P=0.005）， whether or not to have received local treatment （HR=0.63， P=0.014）， and distant metastasis （HR=0.58， P=0.009） were independent risk factors for PFS. There was no significant difference in the incidence rate of AEs between the two groups （P>0.05）.  Conclusion  For patients with unresectable HCC， the triple combination of cryoablation， lenvatinib， and anti-PD-1 monoclonal antibody significantly improves the treatment outcome and survival of patients compared with the double combination of cryoablation and lenvatinib， without increasing AEs， which provides a clinical basis for optimizing the treatment regimen for unresectable HCC.

     

    • FullText(HTML)
  • loading
    • References(28)
  • [1]
    LLOVET JM, de BAERE T, KULIK L, et al. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma[J]. Nat Rev Gastroenterol Hepatol, 2021, 18( 5): 293- 313. DOI: 10.1038/s41575-020-00395-0.
    [2]
    GHAVIMI S, APFEL T, AZIMI H, et al. Management and treatment of hepatocellular carcinoma with immunotherapy: a review of current and future options[J]. J Clin Transl Hepatol, 2020, 8( 2): 168- 176. DOI: 10.14218/JCTH.2020.00001.
    [3]
    LIU YE, ZONG J, CHEN XJ, et al. Cryoablation combined with radiotherapy for hepatic malignancy: Five case reports[J]. World J Gastrointest Oncol, 2020, 12( 2): 237- 247. DOI: 10.4251/wjgo.v12.i2.237.
    [4]
    KIM R, KANG TW, DI CHA, et al. Percutaneous cryoablation for perivascular hepatocellular carcinoma: Therapeutic efficacy and vascular complications[J]. Eur Radiol, 2019, 29( 2): 654- 662. DOI: 10.1007/s00330-018-5617-6.
    [5]
    ABDO J, CORNELL DL, MITTAL SK, et al. Immunotherapy plus cryotherapy: potential augmented abscopal effect for advanced cancers[J]. Front Oncol, 2018, 8: 85. DOI: 10.3389/fonc.2018.00085.
    [6]
    CHEN LT, MARTINELLI E, CHENG AL, et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO[J]. Ann Oncol, 2020, 31( 3): 334- 351. DOI: 10.1016/j.annonc.2019.12.001.
    [7]
    BENSON AB, D’ANGELICA MI, ABBOTT DE, et al. Hepatobiliary cancers, version 2.2021, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2021, 19( 5): 541- 565. DOI: 10.6004/jnccn.2021.0022.
    [8]
    SCHREIBER RD, OLD LJ, SMYTH MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion[J]. Science, 2011, 331( 6024): 1565- 1570. DOI: 10.1126/science.1203486.
    [9]
    CHENG AL, QIN S, IKEDA M, et al. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma[J]. J Hepatol, 2022, 76( 4): 862- 873. DOI: 10.1016/j.jhep.2021.11.030.
    [10]
    PENG Z, FAN W, ZHU B, et al. Lenvatinib combined with transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma: A Phase Ⅲ, Randomized Clinical Trial-LAUNCH)[J]. J Clin Oncol, 2023, 41( 1): 117- 127. DOI: 10.1200/JCO.22.00392.
    [11]
    KUDO M, UESHIMA K, IKEDA M, et al. Randomised, multicentre prospective trial of transarterial chemoembolisation(TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial[J]. Gut, 2020, 69( 8): 1492- 1501. DOI: 10.1136/gutjnl-2019-318934.
    [12]
    DUFFY AG, ULAHANNAN SV, MAKOROVA-RUSHER O, et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma[J]. J Hepatol, 2017, 66( 3): 545- 551. DOI: 10.1016/j.jhep.2016.10.029.
    [13]
    NIU LZ, LI JL, ZENG JY, et al. Combination treatment with comprehensive cryoablation and immunotherapy in metastatic hepatocellular cancer[J]. World J Gastroenterol, 2013, 19( 22): 3473- 3480. DOI: 10.3748/wjg.v19.i22.3473.
    [14]
    YAKKALA C, DENYS A, KANDALAFT L, et al. Cryoablation and immunotherapy of cancer[J]. Curr Opin Biotechnol, 2020, 65: 60- 64. DOI: 10.1016/j.copbio.2020.01.006.
    [15]
    TAN J, LIU T, FAN W, et al. Anti-PD-L1 antibody enhances curative effect of cryoablation via antibody-dependent cell-mediated cytotoxicity mediating PD-L1highCD11b+ cells elimination in hepatocellular carcinoma[J]. Acta Pharm Sin B, 2023, 13( 2): 632- 647. DOI: 10.1016/j.apsb.2022.08.006.
    [16]
    KWAK K, YU B, LEWANDOWSKI RJ, et al. Recent progress in cryoablation cancer therapy and nanoparticles mediated cryoablation[J]. Theranostics, 2022, 12( 5): 2175- 2204. DOI: 10.7150/thno.67530.
    [17]
    VOGEL A, MEYER T, SAPISOCHIN G, et al. Hepatocellular carcinoma[J]. Lancet, 2022, 400( 10360): 1345- 1362. DOI: 10.1016/S0140-6736(22)01200-4.
    [18]
    LU M, ZHANG X, GAO X, et al. Lenvatinib enhances T cell immunity and the efficacy of adoptive chimeric antigen receptor-modified T cells by decreasing myeloid-derived suppressor cells in cancer[J]. Pharmacol Res, 2021, 174: 105829. DOI: 10.1016/j.phrs.2021.105829.
    [19]
    YANG XR, SUN HC, XIE Q, et al. Chinese expert guidance on overall application of lenvatinib in hepatocellular carcinoma[J]. Chin J Dig Surg, 2023, 22( 2): 167- 180. DOI: 10.3760/cma.j.cn115610-20230201-00035.

    杨欣荣, 孙惠川, 谢青, 等. 仑伐替尼肝癌全病程应用中国专家指导意见[J]. 中华消化外科杂志, 2023, 22( 2): 167- 180. DOI: 10.3760/cma.j.cn115610-20230201-00035.
    [20]
    YANG Y, LU Y, WANG C, et al. Cryotherapy is associated with improved clinical outcomes of Sorafenib therapy for advanced hepatocellular carcinoma[J]. Cell Biochem Biophys, 2012, 63( 2): 159- 169. DOI: 10.1007/s12013-012-9353-2.
    [21]
    WANG YY, YANG X, WANG YC, et al. Clinical outcomes of lenvatinib plus transarterial chemoembolization with or without programmed death receptor-1 inhibitors in unresectable hepatocellular carcinoma[J]. World J Gastroenterol, 2023, 29( 10): 1614- 1626. DOI: 10.3748/wjg.v29.i10.1614.
    [22]
    CAO F, YANG Y, SI T, et al. The efficacy of TACE combined with lenvatinib plus sintilimab in unresectable hepatocellular carcinoma: a multicenter retrospective study[J]. Front Oncol, 2021, 11: 783480. DOI: 10.3389/fonc.2021.783480.
    [23]
    CAI M, HUANG W, HUANG J, et al. Transarterial chemoembolization combined with lenvatinib plus PD-1 inhibitor for advanced hepatocellular carcinoma: a retrospective cohort study[J]. Front Immunol, 2022, 13: 848387. DOI: 10.3389/fimmu.2022.848387.
    [24]
    PARK JW, KIM YJ, KIM DY, et al. Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The phase Ⅲ STAH trial[J]. J Hepatol, 2019, 70( 4): 684- 691. DOI: 10.1016/j.jhep.2018.11.029.
    [25]
    MARINELLI B, KIM E, D’ALESSIO A, et al. Integrated use of PD-1 inhibition and transarterial chemoembolization for hepatocellular carcinoma: evaluation of safety and efficacy in a retrospective, propensity score-matched study[J]. J Immunother Cancer, 2022, 10( 6). DOI: 10.1136/jitc-2021-004205.
    [26]
    YUAN Y, HE W, YANG Z, et al. TACE-HAIC combined with targeted therapy and immunotherapy versus TACE alone for hepatocellular carcinoma with portal vein tumour thrombus: a propensity score matching study[J]. Int J Surg, 2023, 109( 5): 1222- 1230. DOI: 10.1097/JS9.0000000000000256.
    [27]
    CUI W, FAN W, HUANG K, et al. Large hepatocellular carcinomas: treatment with transarterial chemoembolization alone or in combination with percutaneous cryoablation[J]. Int J Hyperthermia, 2018, 35( 1): 239- 245. DOI: 10.1080/02656736.2018.1493235.
    [28]
    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.
    • 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(6)  / Tables(5)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (280) PDF downloads(55) 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