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程序性细胞死亡受体1及其配体抑制剂在肝细胞癌治疗中的应用进展

王昭月 魏来 黄缘

王昭月, 魏来, 黄缘. 程序性细胞死亡受体1及其配体抑制剂在肝细胞癌治疗中的应用进展[J]. 临床肝胆病杂志, 2021, 37(2): 437-443. DOI: 10.3969/j.issn.1001-5256.2021.02.040
引用本文: 王昭月, 魏来, 黄缘. 程序性细胞死亡受体1及其配体抑制剂在肝细胞癌治疗中的应用进展[J]. 临床肝胆病杂志, 2021, 37(2): 437-443. DOI: 10.3969/j.issn.1001-5256.2021.02.040
WANG ZY, WEI L, HUANG Y. Advances in the application of programmed death-1/programmed death-ligand 1 inhibitors in the treatment of hepatocellular carcinoma [J]. J Clin Hepatol, 2021, 37(2): 437-443. DOI: 10.3969/j.issn.1001-5256.2021.02.040
Citation: WANG ZY, WEI L, HUANG Y. Advances in the application of programmed death-1/programmed death-ligand 1 inhibitors in the treatment of hepatocellular carcinoma [J]. J Clin Hepatol, 2021, 37(2): 437-443. DOI: 10.3969/j.issn.1001-5256.2021.02.040

程序性细胞死亡受体1及其配体抑制剂在肝细胞癌治疗中的应用进展

DOI: 10.3969/j.issn.1001-5256.2021.02.040
详细信息
    作者简介:

    王昭月(1990—),女,博士,主要从事自身免疫性肝病、脂肪肝、肝癌等相关研究

    通讯作者:

    黄缘,huangy9815@163.com

  • 作者贡献声明:王昭月负责资料分析、撰写论文;魏来负责指导写作思路、修改论文;黄缘负责指导撰写文章、最后定稿。
  • 中图分类号: R735.7

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

  • 摘要: 肝细胞癌(HCC)是我国最常见的恶性肿瘤之一,由于缺乏特异性表现,超过一半的患者在初诊时已处于进展期。靶向治疗和系统化疗是进展期HCC的主要治疗方法,疗效有限。近年来,免疫治疗迅速发展。介绍了免疫检查点抑制剂——程序性细胞死亡受体1及其配体(PD-1/PD-L1)抑制剂在HCC治疗中的现状,归纳了多项临床试验的数据结果,分析了单药治疗及联合治疗的安全性及有效性。通过分析表明,免疫治疗已成为全身系统治疗的重要方法之一,尤其是联合治疗可显著提高HCC的疗效,其安全性亦在可控范围内,是未来发展的重要方向。
  • 图  1  PD-1/PD-L1抑制剂单药或联合治疗HCC的ORR、DCR及TRAEs对比

    表  1  PD-1/PD-L1抑制剂单药治疗在aHCC中的临床试验

    药物 临床试验 分期 治疗线数 入组例数 ORR(%) CR(%) DCR(%) mDOR(月) mOS(月) mPFS(月) TRAEs(%)
    任何级别 3~4级
    Nivolumab CheckMate 040 Ⅰ/Ⅱ - 48 15 6 58 17 15.0 - 83 25
    - 214 20 1 64 9.9 NR 4.0 74 19
    一线 80 20 1 54 17.15 28.6 - 78 29
    二线 ESC组,n=37 19 3 54 19.35 15.0 - 77 18
    EXP组,n=145 14 1 55 16.59 15.6 -
    - 85(亚洲队列) 15 4 49 9.7 14.9 - 74 16
    - 49(Child-Pugh B) 10.2 - 55.1 9.9 7.6 - 51 24.5
    Nivolumabvs Sorafenib CheckMate 459 一线 743(NIVO,n=371;SOR,n=372) 15 vs 7 4 vs 1 55 vs 58 23.3 vs 23.4 16.4 vs 14.7 3.7 vs 3.8 - 22 vs 49
    Pembrolizumab KEYNOTE-224 二线 104 17 1 62 NR 12.9 4.9 73 25
    Pembrolizumabvs安慰剂 KEYNOTE-240 二线 413(PEM,n=278;安慰剂,n=135) 18.3 vs 4.4 2.2 vs 0 62.2 vs 53.3 13.8 vs NR 13.9 vs 10.6 3.0 vs 2.8 60.9 vs 48.5 18.3 vs 7.5
    Camrelizumab(SHR-1210) - 二线 217 14.7 0 44.2 NR 13.8 2.1 - 22
    Durvalumab - Ⅰ/Ⅱ 二线 40(可评估,n=39) 10.3 (n=39) 0 33.3 (n=39) - 13.2 - 80 20
    注:“-”,未提供数据;ORR,客观缓解率;CR,完全缓解;DCR,疾病控制率;mDOR,中位缓解持续时间;mOS,中位总生存期;mPFS,中位无进展生存期;TRAEs,治疗相关不良事件;NR,未达到;ESC,剂量爬坡;EXP,剂量扩展;表格中所列数据均根据实体瘤疗效评价标准1.1版(RECIST v1.1)评估所得。
    下载: 导出CSV

    表  2  PD-1/PD-L1抑制剂联合治疗在aHCC中的临床试验

    药物 临床试验 分期 治疗线数 入组例数 ORR(%) CR(%) DCR(%) mDOR(月) mOS(月) mPFS(月) TRAEs(%)
    任何级别 3~4级
    Pembrolizumab+Lenvatinib KEYNOTE-524/Study 116 Ⅰb 一线 100 36 1 88 12.6 22.0 8.6 95 67
    Nivolumab+Lenvatinib Study 117 Ⅰb 一线 30 76.7 13.3 96.7 - - - 100 -
    Camrelizumab(SHR-1210)+Apatinib - 二线 16(可评估) 50 0 93.8 NR NR 7.2 - -
    Avelumab+Axitinib VEGF Liver 100 Ⅰb 一线 22 13.6 - - - - 5.5 - -
    Atezolizumab+Bevacizumab GO30140 Ⅰb 一线 队列A,n=104 36 12 71 NE 17.1 7.3 88 39
    队列F,n=119
    Atezo+Bev,n=60;
    Atezo,n=59
    20 vs 17 2 vs 5 67 vs 49 NE vs NE - 5.6 vs 3.4 68 vs 41 20 vs 5
    Atezolizumab+Bevacizumabvs Sorafenib IMBrave 150 一线 501Atezo+Bev,n=336;
    SOR,n=165
    27.3 vs 11.9 5.5 vs 0 73.6 vs 55.3 NE vs 6.3 NE vs 13.2 6.8 vs 4.3 84 vs 94 36 vs 46
    194(中国人群)
    Atezo+Bev,n=133;
    SOR,n=61
    25 vs 7 - - - NE vs 11.4 5.7 vs 3.2 - -
    Nivolumab+Ipilimumab CheckMate 040 Ⅰ/Ⅱ 二线 148 31 4.7 49 17.5 - - - 37
    A组,n=50 32 8 54 17.5 22.8
    B组,n=49 31 6 43 22.2 12.5
    C组,n=49 31 0 49 16.6 12.7
    Durvalumab+Tremelimumab - - T300+D,n=75 22.7 - - NR 18.7 - - 35.1
    T75+D,n=84 9.5 - - 13.2 11.3 - - 24.4
    Camrelizumab+FOLFOX4 - 一线 34 26.5 - 79.4 NR NR 5.5 - 85.3
    Nivolumab+Cabozantinib±Ipilimumab CheckMate 040 Ⅰ/Ⅱ - 71二联,n=36三联,n=35 17 vs 26 0 vs 0 81 vs 83 - NR vs NR 5.5 vs 6.8 - 42 vs 71
    注:NE,无法评估;表格中所列数据均根据RECIST v1.1评估所得;Atezo, Atezolizumab; Bev, Bevacizumab; SOR, Sorafenib。
    下载: 导出CSV
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  • 收稿日期:  2020-06-22
  • 修回日期:  2020-09-18
  • 刊出日期:  2021-02-20
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