留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

程序性细胞死亡受体1抑制剂联合仑伐替尼治疗晚期原发性肝癌的效果及不良反应

滕颖 丁晓燕 李文东 陈京龙

滕颖, 丁晓燕, 李文东, 等. 程序性细胞死亡受体1抑制剂联合仑伐替尼治疗晚期原发性肝癌的效果及不良反应[J]. 临床肝胆病杂志, 2021, 37(3): 606-610. DOI: 10.3969/j.issn.1001-5256.2021.03.020
引用本文: 滕颖, 丁晓燕, 李文东, 等. 程序性细胞死亡受体1抑制剂联合仑伐替尼治疗晚期原发性肝癌的效果及不良反应[J]. 临床肝胆病杂志, 2021, 37(3): 606-610. DOI: 10.3969/j.issn.1001-5256.2021.03.020
TENG Y, DING XY, LI WD, et al. Clinical effect of programmed cell death-1 inhibitor combined with lenvatinib in treatment of advanced primary liver cancer and related adverse events [J]. J Clin Hepatol, 2021, 37(3): 606-610. DOI: 10.3969/j.issn.1001-5256.2021.03.020
Citation: TENG Y, DING XY, LI WD, et al. Clinical effect of programmed cell death-1 inhibitor combined with lenvatinib in treatment of advanced primary liver cancer and related adverse events [J]. J Clin Hepatol, 2021, 37(3): 606-610. DOI: 10.3969/j.issn.1001-5256.2021.03.020

程序性细胞死亡受体1抑制剂联合仑伐替尼治疗晚期原发性肝癌的效果及不良反应

DOI: 10.3969/j.issn.1001-5256.2021.03.020
基金项目: 

首都临床特色应用研究 Z181100001718131

详细信息
    作者简介:

    滕颖(1985—),女,博士,主要从事肝癌基础及临床研究

    通讯作者:

    陈京龙,chejl6412@sina.com

  • 利益冲突声明:本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突,特此声明。
  • 作者贡献声明:滕颖、陈京龙负责课题设计,资料分析,撰写论文;滕颖、丁晓燕、李文东参与收集数据,修改论文;陈京龙负责拟定写作思路,指导撰写文章并最后定稿。
  • 中图分类号: R735.7

Clinical effect of programmed cell death-1 inhibitor combined with lenvatinib in treatment of advanced primary liver cancer and related adverse events

  • 摘要:   目的  初步探索国产程序性细胞死亡受体1(PD-1)抑制剂联合仑伐替尼在晚期原发性肝癌治疗中的临床疗效及不良反应。  方法  回顾性分析2019年1月1日—2020年4月2日于首都医科大学附属北京地坛医院使用国产PD-1抑制剂联合仑伐替尼治疗的24例晚期肝癌患者的临床资料,其中卡瑞利珠单抗联合仑伐替尼治疗组15例,信迪利单抗联合仑伐替尼治疗组7例,特瑞普利单抗联合仑伐替尼组2例。随访患者,肝内病灶使用mRECIST标准、肝外转移灶采用RECIST1.1标准评价疗效。Kaplan-Meier法绘制生存曲线。  结果  24例肝癌患者中,11例疗效评价为部分缓解,7例疗效评价为疾病稳定,6例疗效评价为疾病进展,客观缓解率为45.8%,疾病控制率为75.0%。中位疾病进展时间为8.40个月(95%CI:6.89~9.91个月)。不良反应发生率为54.17%,最常见的不良反应为疲乏(29.17%)、高血压(25.00%)。  结论  PD-1抑制剂联合仑伐替尼治疗晚期肝癌临床效果显著,严重不良反应发生率低,是一种安全、有效的治疗方案。
  • 图  1  TTP的生存曲线分析

    图  2  OS的生存曲线分析

    表  1  24例入组患者临床资料

    项目 数值
    年龄[例(%)]
      ≤50岁 8(33.3)
      >50岁 16(66.7)
    性别[例(%)]
      男 19(79.2)
      女 5(20.8)
    病毒感染[例(%)]
      HBV 19(79.2)
      HCV 2(8.3)
      无 3(12.5)
    肝硬化[例(%)]
      有 17(70.8)
       无 7(29.2)
    Child-Pugh分级[例(%)]
      A级 18(75.0)
      B级 6(25.0)
    AFP水平[例(%)]
      <200 ng/ml 14(58.3)
      ≥200 ng/ml 10(41.7)
    门静脉癌栓[例(%)]
      Ⅰ 0
      Ⅱ 8(33.3)
      Ⅲ 4(16.7)
      Ⅳ 3(12.5)
    转移部位[例(%)]
      淋巴结Ⅳ 12(50.0)Ⅳ
      腹腔Ⅳ 5(20.8)Ⅳ
      肺 3(12.5)
    治疗情况[例(%)]
      一线Ⅳ 11(45.8)Ⅳ
      二线Ⅳ 11(45.8)Ⅳ
      三线 (8.3)
    下载: 导出CSV

    表  2  24例入组患者不良反应情况

    项目 合计[例(%)] 1级[例(%)] 2级[例(%)] 3级[例(%)]
    食欲下降 3(12.50) 3(12.50)
    体质量下降 1(4.17) 1(4.17)
    疲乏 7(29.17) 4(16.67) 2(8.33) 1(4.17)
    腹泻 3(12.50) 2(8.33) 1(4.17)
    皮肤毛细血管增生症 1(4.17) 1(4.17)
    皮疹 3(12.50) 1(4.17) 1(4.17) 1(4.17)
    手足综合征 1(4.17) 1(4.17)
    高血压 6(25.00) 1(4.17) 3(12.50) 2(8.33)
    胆红素升高 1(4.17) 1(4.17)
    尿蛋白 3(12.50) 3(12.50)
    急性肾损伤 2(8.33) 1(4.17) 1(4.17)
    肾上腺皮质功能减退 1(4.17) 1(4.17)
    甲状腺功能减退 3(12.50) 2(8.33) 1(4.17)
    下载: 导出CSV
  • [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] ZHENG R, QU C, ZHANG S, et al. Liver cancer incidence and mortality in China: Temporal trends and projections to 2030[J]. Chin J Cancer Res, 2018, 30(6): 571-579. DOI: 10.21147/j.issn.1000-9604.2018.06.01
    [3] LLOVET JM, MONTAL R, SIA D, et al. Molecular therapies and precision medicine for hepatocellular carcinoma[J]. Nat Rev Clin Oncol, 2018, 15(10): 599-616. DOI: 10.1038/s41571-018-0073-4
    [4] GRETEN TF, PAPENDORF F, BLECK JS, et al. Survival rate in patients with hepatocellular carcinoma: A retrospective analysis of 389 patients[J]. Br J Cancer, 2005, 92(10): 1862-1868. DOI: 10.1038/sj.bjc.6602590
    [5] 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
    [6] TOPALIAN SL, HODI FS, BRAHMER JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer[J]. N Engl J Med, 2012, 366(26): 2443-2454. DOI: 10.1056/NEJMoa1200690
    [7] 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
    [8] 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
    [9] FUKUMURA D, KLOEPPER J, AMOOZGAR Z, et al. Enhancing cancer immunotherapy using antiangiogenics: Opportunities and challenges[J]. Nat Rev Clin Oncol, 2018, 15(5): 325-340. DOI: 10.1038/nrclinonc.2018.29
    [10] KATO Y, TABATA K, KIMURA T, et al. Lenvatinib plus anti-PD-1 antibody combination treatment activates CD8+ T cells through reduction of tumor-associated macrophage and activation of the interferon pathway[J]. PLoS One, 2019, 14(2): e0212513. DOI: 10.1371/journal.pone.0212513
    [11] 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
    [12] LENCIONI R, LLOVET JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma[J]. Semin Liver Dis, 2010, 30(1): 52-60. DOI: 10.1055/s-0030-1247132
    [13] EISENHAUER EA, THERASSE P, BOGAERTS J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)[J]. Eur J Cancer, 2009, 45(2): 228-247. DOI: 10.1016/j.ejca.2008.10.026
    [14] WANG F, QIN S, SUN X, et al. Reactive cutaneous capillary endothelial proliferation in advanced hepatocellular carcinoma patients treated with camrelizumab: Data derived from a multicenter phase 2 trial[J]. J Hematol Oncol, 2020, 13(1): 47. DOI: 10.1186/s13045-020-00886-2
    [15] HOOS A. Development of immuno-oncology drugs-from CTLA4 to PD1 to the next generations[J]. Nat Rev Drug Discov, 2016, 15(4): 235-247. DOI: 10.1038/nrd.2015.35
    [16] SHEN H, YANG ES, CONRY M, et al. Predictive biomarkers for immune checkpoint blockade and opportunities for combination therapies[J]. Genes Dis, 2019, 6(3): 232-246. DOI: 10.1016/j.gendis.2019.06.006
    [17] 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
    [18] RIVERA LB, MEYRONET D, HERVIEU V, et al. Intratumoral myeloid cells regulate responsiveness and resistance to antiangiogenic therapy[J]. Cell Rep, 2015, 11(4): 577-591. DOI: 10.1016/j.celrep.2015.03.055
    [19] YASUDA S, SHO M, YAMATO I, et al. Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2(VEGFR2) induces synergistic anti-tumour effect in vivo[J]. Clin Exp Immunol, 2013, 172(3): 500-506. DOI: 10.1111/cei.12069
    [20] KIMURA T, KATO Y, OZAWA Y, et al. Immunomodulatory activity of lenvatinib contributes to antitumor activity in the Hepa1-6 hepatocellular carcinoma model[J]. Cancer Sci, 2018, 109(12): 3993-4002. DOI: 10.1111/cas.13806
    [21] CHEN J, HU X, LI Q, et al. Effectiveness and safety of toripalimab, camrelizumab, and sintilimab in a real-world cohort of hepatitis B virus associated hepatocellular carcinoma patients[J]. Ann Transl Med, 2020, 8(18): 1187. DOI: 10.21037/atm-20-6063
  • 加载中
图(2) / 表(2)
计量
  • 文章访问数:  48
  • HTML全文浏览量:  22
  • PDF下载量:  17
  • 被引次数: 0
出版历程
  • 收稿日期:  2020-09-12
  • 修回日期:  2020-10-26
  • 刊出日期:  2021-03-16
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回