化疗联合PD-1/PD-L1抑制剂治疗三阴性乳腺癌有效性和安全性的Meta分析

Efficacy and safety of chemotherapy combined with PD-1/PD-L1 inhibitors in the treatment of triple-negative breast cancer:A Meta-analysis

目的:利用循证医学手段,通过Meta分析评估化疗联合PD-1/PD-L1抑制剂与单纯化疗治疗三阴性乳腺癌的安全性和有效性,从而为临床诊疗提供指导意见。方法:检索Pubmed、Embase、Cochrane图书馆、知网、万方、维普和CBM数据库从建库到2021年08月以来有关化疗联合PD-1/PD-L1抑制剂治疗三阴性乳腺癌的文献。由两位研究者独立完成筛选文献、提取资料以及评估偏倚风险后,采用RevMan 5.3和STATA 15.1软件进行统计分析。结果:本次研究共纳入8篇文献。汇总结果表明联合治疗组患者的总生存期(overall survival,OS)和无进展生存期(progression-free survival,PFS)明显长于仅接受化疗的患者(HR=0.85,95%CI:0.75~0.96;HR=0.84,95%CI:0.73~0.97)。结果还表明联合治疗组患者的(complete remission rate,CRR)也显著高于仅接受化疗治疗的患者(RR=1.44,95%CI:1.10~1.89)。此外,联合治疗组的不良反应发生率高于单纯化疗组(RR=1.08,95%CI:1.03~1.14)。亚组分析的结果显示接受Atezolizumab联合化疗的患者的OS明显长于单独接受化疗的患者(HR=0.85,95%CI:0.75~0.96),接受Atezolizumab或Pembrolizumab与化疗的联合治疗显著延长了患者的PFS(HR=0.80,95%CI:0.73~0.89;HR=0.79,95%CI:0.67~0.92),然而接受Durvalumab联合化疗的患者OS和PFS较单纯化疗并无显著差异。结论:化疗联合PD-1/PD-L1抑制剂治疗三阴性乳腺癌比单独化疗更有效,但联合治疗有着更高的不良反应发生率。此外,Durvalumab与化疗药的联合使用并不能增加患者的OS和PFS。

Objective:To evaluate the efficacy and safety of chemotherapy combined with PD-1/PD-L1 inhibitors and chemotherapy alone in the treatment of triple-negative breast cancer by using Meta-analysis,so as to provide guidance for clinical diagnosis and treatment.Methods:Searching Pubmed,Embase,Cochrane Library,CNKI,Wanfang,CQVIP and CBM databases from the establishment of the database to Aug 2021 on the literature on chemotherapy combined with PD-1/PD-L1 inhibitors in the treatment of triple-negative breast cancer.After two researchers independently completed the screening of literature,extracting data,and assessing the risk of bias,RevMan 5.3 software was used for statistical analysis.Results:A total of 8 articles were included in this study.The summary results showed that the OS and PFS of patients in the combination treatment group were significantly longer than those of patients receiving chemotherapy only(HR=0.85,95%CI:0.75~0.96;HR=0.84,95%CI:0.73~0.97).The results also showed that the CRR of patients in the combination therapy group was also significantly higher than that of patients receiving chemotherapy only(RR=1.44,95%CI:1.10~1.89).In addition,the incidence of adverse events in the combined treatment group was higher than that in the chemotherapy alone group(RR=1.08,95%CI:1.03~1.14).The results of the subgroup analysis showed that the OS of patients receiving atezolizumab combined with chemotherapy was significantly longer than that of patients receiving chemotherapy alone(HR=0.85,95%CI:0.75~0.96).In addition,the combination therapy of atezolizumab or pembrolizumab and chemotherapy significantly prolonged the patient’s PFS(HR=0.80,95%CI:0.73~0.89;HR=0.79,95%CI:0.67~0.92).However,there was no significant difference in OS and PFS in patients receiving durvalumab combined with chemotherapy compared with chemotherapy alone.Conclusion:These results indicate that chemotherapy combined with PD-1/PD-L1 inhibitors is more effective in the treatment of triple-negative breast cancer than chemotherapy alone,but the combination therapy has a higher incidence of adverse reactions,which deserves our attention.In addition,the combination of durvalumab and chemotherapeutics did not increase the patient’s OS and PFS.