免疫检查点抑制剂治疗转移性结直肠癌疗效与安全性的Meta分析  

Meta-analysis of the efficacy and safety of immune checkpoint inhibitors in the treatment of metastatic colorectal cancer

作　　者：陈威 陈嘉怡 李铃 余俊先[1] CHEN Wei;CHEN Jiayi;LI Ling;YU Junxian(Dept.of Pharmacy,Beijing Friendship Hospital Affiliated to Capital Medical University,Beijing 100050,China;School of Nursing,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学附属北京友谊医院药学部,北京100050 [2]首都医科大学护理学院,北京100069

出　　处：《中国药房》2023年第4期482-486,共5页China Pharmacy

摘　　要：目的系统评价免疫检查点抑制剂(ICIs)治疗转移性结直肠癌(mCRC)的疗效和安全性,旨在为临床用药提供循证参考。方法计算机检索PubMed、the Cochrane Library、Web of Science、Embase、中国知网、万方数据、维普网,收集ICIs(试验组)对比传统化疗或最佳支持治疗(对照组)的随机对照试验(RCT),检索时限为建库起至2022年6月1日。筛选文献,提取资料后,采用Co‐chrane系统评价员手册5.1.0推荐的偏倚风险评估工具对纳入文献质量进行评价;采用RevMan 5.4软件进行Meta分析和敏感性分析。结果共纳入4项RCT,合计833例患者。Meta分析结果显示,试验组患者的总生存期(OS)[HR=0.77,95%CI(0.64,0.94),P=0.01]、无进展生存期(PFS)[HR=0.67,95%CI(0.57,0.79),P<0.00001]均显著高于对照组;两组患者的3级及以上不良事件发生率比较,差异无统计学意义[RR=1.22,95%CI(0.77,1.94),P=0.39]。按突变模式的不同进行的亚组分析结果显示,试验组中错配修复熟练且低水平微卫星不稳定(pMMR-MSS)mCRC患者的PFS显著高于对照组(P<0.05)。敏感性分析结果显示,本研究所得结果稳健。结论与传统化疗或最佳支持治疗比较,ICIs可延长mCRC患者的OS和PFS,且在pMMR-MSS mCRC患者中可能更具优势;ICIs与传统化疗或最佳支持治疗的安全性相当。OBJECTIVE To systematically evaluate the efficacy and safety of immune checkpoint inhibitors(ICIs)in the treatment of metastatic colorectal cancer(mCRC),so as to provide evidence-based reference for clinical practice.METHODS PubMed,the Cochrane Library,Web of Science,Embase,CNKI,Wanfang and VIP databases were searched to collect randomized controlled trials(RCT)of ICIs(trial group)versus traditional chemotherapy or optimal supportive treatment(control group)in the treatment of mCRC from the establishment of the database to June 1,2022.After literature screening and data extraction,Cochrane Systematic Review Manual 5.1.0 was used to evaluate the quality of the included literature,and RevMan 5.4 software was used for meta-analysis and sensitivity analysis.RESULTS A total of 4 RCTs were included,involving 833 patients.Meta-analysis showed that the overall survival(OS)[HR=0.77,95%CI(0.64,0.94),P=0.01]and progression-free survival(PFS)[HR=0.67,95%CI(0.57,0.79),P<0.00001]were significantly higher in trial group than control group;the difference was not statistically significant when comparing the incidence of grade 3 and above adverse events in the two groups[RR=1.22,95%CI(0.77,1.94),P=0.39].Subgroup analysis by mutation pattern showed that patients with mismatch repair proficiency and low levels of microsatellite instability(pMMR-MSS)mCRC patients in trial group had significantly higher PFS than control group(P<0.05).The results of sensitivity analysis showed that the results were robust.CONCLUSIONS Compared with traditional chemotherapy or optimal supportive treatment,ICIs can prolong the OS and PFS of mCRC patients,and maybe has more advantages in pMMR-MSS mCRC patients;the safety of ICIs is equivalent to that of traditional chemotherapy or optimal supportive treatment.

关 键 词：免疫检查点抑制剂 转移性结直肠癌 META分析 疗效 安全性 

分 类 号：R734.2[医药卫生—肿瘤] R979.1[医药卫生—临床医学]