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程序性细胞死亡受体-1抑制剂治疗中晚期非病毒性相关肝癌的效果及安全性分析

刘浩楠 王玉芹 吴萌 陆通 赵阳 韩正祥

引用本文:
Citation:

程序性细胞死亡受体-1抑制剂治疗中晚期非病毒性相关肝癌的效果及安全性分析

DOI: 10.3969/j.issn.1001-5256.2022.12.015
基金项目: 

江苏省高层次卫生人才“六个一工程”A类项目 LGY2020006

伦理学声明:本研究于2022年6月23日得到徐州医科大学附属医院伦理委员会的批准,批准文号:XYFY2022-KL207-01。患者均在使用PD-1抑制剂之前签署知情同意书。
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。
作者贡献声明:刘浩楠、王玉芹、韩正祥对研究的思路或设计有关键贡献;吴萌、陆通参与了研究数据的获取;刘浩楠、赵阳完成了数据分析;韩正祥修改文章关键内容并定稿。
详细信息
    通信作者:

    韩正祥,cnhzxyq@163.com

Effectiveness and safety of programmed cell death-1 inhibitor in the treatment of advanced non-HBV non-HCV-related hepatocellular carcinoma

Research funding: 

Jiangsu Province High-level Health Talents "Six Ones Project" Category A Project LGY2020006

More Information
    Corresponding author: HAN Zhengxiang, cnhzxyq@163.com (ORCID: 0000-0002-1199-8983)
  • 摘要:   目的  研究国产程序性细胞死亡受体-1(PD-1)抑制剂在中晚期非病毒性相关肝癌(NBNC-HCC)中的临床疗效及不良反应。  方法  选取2019年6月—2022年2月徐州医科大学附属医院收治的使用国产PD-1抑制剂治疗的31例中晚期NBNC-HCC患者。分析患者疾病进展时间、客观缓解率、疾病控制率和不良反应发生情况。采用Kaplan-Meier法绘制生存曲线。  结果  在31例中晚期NBNC-HCC患者中,1例患者疗效评价为完全缓解,4例评价为部分缓解,6例评价为疾病稳定,20例评价为疾病进展,客观缓解率为16.1%,疾病控制率为35.5%,中位疾病进展时间为7.2(6.4~8.0)个月。不良反应发生率为61.30%,常见的不良反应为皮疹(29.03%)和高血压(22.58%),所有患者均无4级不良反应和不良反应相关死亡事件发生。  结论  本研究提示中晚期NBNC-HCC患者对PD-1抑制剂治疗的反应可能较弱,但不良反应可控,未来仍需多中心前瞻性试验进一步验证。

     

  • 图  1  TTP的生存曲线分析

    Figure  1.  Survival curve analysis of TTP

    图  2  OS的生存曲线分析

    Figure  2.  Survival curve analysis of OS

    表  1  入组患者的临床资料

    Table  1.   Clinical information of enrolled patients

    项目 数值
    年龄(岁) 57.13±11.55
    性别[例(%)]
      男 20(64.5)
      女 11(35.5)
    病因[例(%)]
      NAFLD 24(77.4)
      酒精性肝病 6(19.4)
      自身免疫性肝病 1(3.2)
    肿瘤大小[例(%)]
      <5 cm 13(41.9)
      ≥5 cm 18(58.1)
    门静脉浸润[例(%)]
      有 22(71.0)
      无 9(29.0)
    肝外转移[例(%)]
      有 13(41.9)
      无 18(58.1)
    Child-Pugh分级[例(%)]
      A 23(74.2)
      B 8(25.8)
    BCLC分期[例(%)]
      B 5(16.1)
      C 26(83.9)
    ECOG评分[例(%)]
      0 3(9.7)
      1 22(71.0)
      2 6(19.4)
    既往治疗方式[例(%)]
      TACE 19(61.3)
      手术 6(19.4)
      射频消融 4(12.9)
      仑伐替尼 13(41.9)
      索拉非尼 9(29.0)
      阿帕替尼 6(19.4)
      沙利度胺 8(25.8)
      无 3(9.7)
    PD-1抑制剂[例(%)]
      卡瑞利珠单抗 18(58.1)
      信迪利单抗 9(29.0)
      特瑞普利单抗 4(12.9)
    注:NAFLD,非酒精性脂肪性肝病;TACE,经导管动脉化疗栓塞术。
    下载: 导出CSV

    表  2  入组患者的实验室资料

    Table  2.   Laboratory information of enrolled patients

    项目 数值
    AFP[例(%)]
      <400 ng/mL 13(42.0)
      ≥400 ng/mL 18(58.0)
    AST(U/L) 36.87±14.64
    ALT(U/L) 27.74±13.32
    Alb(g/L) 39.55±5.01
    TBil(μmol/L) 17.57±8.76
    PT(s) 12.04±1.05
    下载: 导出CSV

    表  3  入组患者肿瘤应答情况

    Table  3.   Tumor response of enrolled patients

    项目 数值
    CR(例) 1
    PR(例) 4
    SD(例) 6
    PD(例) 20
    ORR(%) 16.1(5/31)
    DCR(%) 35.5(11/31)
    下载: 导出CSV

    表  4  所有患者的不良反应情况

    Table  4.   Incidence of adverse reactions in all patients

    项目 3级不良反应 总不良反应
    皮疹[例(%)] 2(6.45) 9(29.03)
    腹泻[例(%)] 1(3.23) 5(16.13)
    疲劳[例(%)] 1(3.23) 6(19.35)
    恶心[例(%)] 0 4(12.90)
    蛋白尿[例(%)] 1(3.23) 5(16.13)
    甲状腺炎[例(%)] 1(3.23) 3(9.68)
    感觉异常[例(%)] 0 2(6.45)
    高血压[例(%)] 3(9.68) 7(22.58)
    口腔溃疡[例(%)] 0 4(12.90)
    胆红素升高[例(%)] 0 2(6.45)
    反应性皮肤毛细血管增生症[例(%)] 0 2(6.45)
    ALT升高[例(%)] 0 4(12.90)
    AST升高[例(%)] 1(3.23) 2(6.45)
    肾上腺皮质功能减退[例(%)] 0 2(6.45)
    下载: 导出CSV
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  • 收稿日期:  2022-06-11
  • 录用日期:  2022-07-12
  • 出版日期:  2022-12-20
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