中国实用外科杂志

中国实用外科杂志

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程序性细胞死亡蛋白-1抑制剂治疗晚期胆道恶性肿瘤疗效和预后因素分析

王敬晗1a,2[Author]) AND 1[Journal]) AND year[Order])" target="_blank">2，李    炜1a,3，马文聪1a,2[Author]) AND 1[Journal]) AND year[Order])" target="_blank">2，宋    浩1b，敖建阳1a，李    斌1a，冯飞灵1a，程庆保1a，于    勇1a，吴小兵1a，易    滨1b，刘    辰1a，姜小清1a   

  1. 1海军军医大学东方肝胆外科医院    a.胆道一科  b.肝移植科，上海 200438；2同济大学附属东方医院肝胆胰外科，上海200120；3上海中医药大学附属普陀医院普外科，上海 200062
  • 出版日期:2021-05-01 发布日期:2021-05-17

  • Online:2021-05-01 Published:2021-05-17

摘要： 目的    评估程序性细胞死亡蛋白-1（PD-1）抑制剂治疗晚期胆道恶性肿瘤（BTC）的有效性和安全性。方法    回顾性分析2017年1月至2020年1月92例海军军医大学东方肝胆外科医院胆道一科接受PD-1 抑制剂治疗的晚期BTC病人临床资料、治疗效果、疾病无进展生存期（PFS）、总生存期（OS）和药物不良反应等资料，探讨不同治疗方案的临床疗效及可能相关的预后因素。结果    92例病人中，胆囊癌（GBC）31例、肝内胆管癌（ICC）34例、肝外胆管癌（ECC）27例。PD-1抑制剂治疗后6个月的客观缓解率（ORR）和疾病控制率分别为（DCR）17.4％和40.2％，其中GBC（25.8%）和ICC（23.5%）病人的ORR高于ECC（0）病人。92例病人的中位PFS为4.0个月，中位OS为10.0个月。联合靶向治疗组中位PFS及OS大于单药组（分别为5.0 个月vs. 2.5个月，P=0.007；11.0 vs. 7.5个月，P=0.005），差异有统计学意义；联合化疗组中位PFS 及OS大于单药组，但差异无统计学意义（分别为3.2 个月vs. 2.5个月，P=0.227；10.0个月 vs. 7.5个月，P=0.114）；联合靶向治疗组中位PFS 及OS与联合化疗组相比，差异无统计学意义（分别为5.0个月vs. 3.2个月，P=0.101；11.0 vs. 10.0个月，P=0.254）。6例病人出现3级及以上免疫相关的不良反应。结论    对于晚期BTC病人，PD-1抑制剂联合靶向治疗的效果优于单药治疗；与ECC相比，GBC和ICC病人更可能从PD-1抑制剂治疗中获益。

关键词: 胆道恶性肿瘤, 免疫治疗, 免疫检查点抑制剂, 程序性细胞死亡蛋白-1, 程序性细胞死亡配体-1

Abstract: Efficacy and prognostic factors of programmed cell death protein-1  inhibitors in the treatment of advanced biliary tract cancer        WANG Jing-han ，LI Wei ，MA Wen-cong ，et al. Department of Biliary Tract Surgery I,  Eastern Hepatobiliary Surgery Hospital,  the Second Military Medical University, Shanghai 200438, China
Corresponding author: JIANG Xiao-qing , E-mail: jxq1225@sina.com
WANG Jing-han and LI  Wei are the first authors who contributed equally to the article
Abstract    Objective    To evaluate the efficacy and safety of programmed cell death protein-1 inhibitors in the treatment of advanced biliary tract cancer (BTC). Methods    The clinical data, treatment effects, progression free survival (PFS), overall survival (OS) and adverse events of 92 patients with advanced BTC who received programmed cell death protein-1 inhibitors treatment in the Department of Biliary Tract Surgery I, Eastern Hepatobiliary Surgery Hospital from January 2017 to January 2020 were retrospectively analyzed to explore the clinical efficacy among different treatment options and possible prognostic factors. Results    Among 92 patients, gallbladder cancer (GBC) were 31 cases, intrahepatic cholangiocarcinoma (ICC) were 34 cases, extrahepatic cholangiocarcinoma (ECC) were 27 cases. The ORR and DCR at 6 months after programmed cell death protein-1 inhibitors treatment were 17.4％ and 40.2% respectively. The ORR of GBC (25.8%) and ICC (23.5%) patients was significantly higher than that of ECC (0%) patients.  The median PFS and OS of 92 patients were 4.0 months and 10.0 months respectively. The median PFS （5.0 months vs. 2.5 months，P=0.007）and OS （11.0 months vs. 7.5 months，P=0.005）in group of combined with targeted therapy were significantly better than those in monotherapy group, while patients in group combined with chemotherapy had better median PFS （3.2 months vs. 2.5 months，P=0.227）and OS （10.0 months vs. 7.5 months，P=0.114）compared with those in monotherapy group, but there was no significant difference. The median PFS （5.0 months vs. 3.2 months，P=0.101）and OS （11.0 months vs. 10.0 months，P=0.254）between groups of combined with targeted therapy and combined with chemotherapy did not show significant difference. Six patients had immune-related adverse events above grade 3. Conclusion    For patients with advanced BTC, the effect of programmed cell death protein-1 inhibitors combined with targeted therapy is better than programmed cell death protein-1 inhibitors monotherapy. Compared with ECC, patients with GBC and ICC may achieve more benefits from immunotherapy .

Key words: biliary tract cancer, immunotherapy, immune checkpoint inhibitors , programmed cell death protein-1, programmed cell death ligand-1