奥拉帕利辅助治疗BRCA1/2突变HER2阴性乳腺癌有效性与安全性的Meta分析

Efficacy and safety of olaparib in adjuvant therapy of BRCA1/2 mutated HER2-negative breast cancer:a meta-analysis

目的系统评价奥拉帕利辅助治疗乳腺癌易感基因(BRCA)1/2突变人表皮生长因子受体2(HER2)阴性乳腺癌的有效性和安全性,为临床治疗提供循证参考。方法计算机检索中国知网、维普、万方、PubMed、ScienceDirect、the Cochrane Library和Embase数据库,收集奥拉帕利辅助治疗(试验组)对比其他药物辅助治疗(对照组)的随机对照试验。筛选文献、提取数据后,采用RevMan 5.4软件进行Meta分析、发表偏倚分析和敏感性分析。结果共纳入5项随机对照试验,共计2633例患者,其中试验组1459例,对照组1174例。Meta分析结显示,在有效性方面,与对照组相比,试验组患者的总生存期[HR=1.02,95%CI(1.01,1.03),P=0.0008]和无进展生存期[HR=1.78,95%CI(1.46,2.17),P<0.00001]显著延长。在安全性方面,与对照组相比,试验组患者的任何级别不良反应发生率更高[RR=1.41,95%CI(1.12,1.78),P=0.004],而两组患者的3级以上不良反应发生率比较差异无统计学意义[RR=1.75,95%CI(0.82,3.74),P=0.15]。发表偏倚结果显示,本研究存在发表偏倚的可能性较小。敏感性分析结果显示,本研究所得结果稳健。结论与非奥拉帕利辅助治疗的患者相比,奥拉帕利辅助治疗BRCA1/2突变HER2阴性乳腺癌可延长患者的总生存期和无进展生存期,但不良反应发生风险相对较高。

OBJECTIVE To systematically evaluate the efficacy and safety of olaparib in adjuvant therapy of breast cancer susceptibility gene(BRCA)1/2 mutated human epidermal growth factor receptor 2(HER2)-negative breast cancer,and to provide evidence-based reference for clinical treatment.METHODS Retrieved from CNKI,VIP,Wanfang data,PubMed,ScienceDirect,the Cochrane Library and Embase databases,randomized controlled trials about adjuvant therapy of olaparib(trial group)versus adjuvant therapy of other drugs(control group)were collected.After literature screening and data extraction,meta-analysis,publication bias analysis and sensitivity analysis were performed by using RevMan5.4 software.RESULTS A total of 5 randomized controlled trials were included,with a total of 2633 patients,including 1495 cases in trial group and 1174 cases in control group.Meta-analysis showed that in terms of efficacy,compared with control group,overall survival[HR=1.02,95%CI(1.01,1.03),P=0.0008]and progression-free survival[HR=1.78,95%CI(1.46,2.17),P<0.00001]were longer significantly in the trial group.In terms of safety,compared with the control group,the incidence of adverse drug reactions at any level in the trial group was higher[RR=1.41,95%CI(1.12,1.78),P=0.004],while there was no statistically significant difference in the incidence of adverse drug reactions above level 3 between the two groups[RR=1.75,95%CI(0.82,3.74),P=0.15].The results of publication bias indicated that the possibility of publication bias in this study was relatively low.The results of sensitivity analysis showed that the results obtained in this study were robust.CONCLUSIONS Compared with patients without adjuvant therapy of olaparib,adjuvant therapy of olaparib can prolong overall survival and progression-free survival of patients with BRCA1/2 mutated HER2-negative breast cancer,but the risk of adverse drug reactions is relatively high.