奥希替尼对非小细胞肺癌脑转移疗效及安全性的meta分析

Safety and efficacy of osimertinib for brain metastases from non-small cell lung cancer:a meta analysis

目的评价奥希替尼治疗非小细胞肺癌(NSCLC)脑转移的有效性和安全性。方法通过计算机检索中国知网、万方数据库、维普数据库、中国生物医学文献服务系统(CBM)、EMBASE、PubMed、Cochrane Library、Clinicaltrials、ScienceDirect等数据库,按照纳入排除标准收集奥希替尼治疗NSCLC脑转移的临床试验,检索时间为从建库至2019年3月。主要结局指标包括疾病控制率(DCR)、客观缓解率(ORR)、无进展生存时间(PFS)及不良反应;采用率差(RD)和风险比(HR)为效应量,采用RevMan 5.3软件进行meta分析。结果共纳入6篇文献,共1726例NSCLC患者,其中脑转移409例。Meta分析表明:在疗效方面,相较于单纯化疗、标准表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKIs),奥希替尼治疗脑转移降低了疾病进展风险(HR=0.32,95%CI:0.15~0.68,P<0.05;HR=0.48,95%CI:0.26~0.88,P<0.05),提高了DCR(RD=0.87,95%CI:0.82~0.91,P<0.05)和ORR(RD=0.44,95%CI:0.37~0.50,P<0.05);在安全性方面,奥希替尼引起3级及以上不良反应的发生率比标准EGFR-TKIs或单化疗低(RR=0.44,95%CI:0.22~0.47,P<0.05;RR=0.78,95%CI:0.62~0.97,P<0.05)。结论奥希替尼相较于其他治疗方案脑转移进展的风险降低,明显延长了PFS,并且DCR、ORR较好,3级及以上不良反应发生率较低。

Objective To evaluate the efficacy and safety of osimertinib in the treatment of brain metastases from non-small-cell lung cancer(NSCLC).Methods Retrieved from CNKI,Wanfang database,VIP database,CBM,EMBASE,PubMed,the Cochrane Library,Clinicaltrials,ScienceDirect and other databases,according to the inclusion and exclusion criteria,clinical trials about osimertinib in the treatment of brain metastases from NSCLC were collected from inception to March 2019.The main outcome indicators included disease control rate(DCR),objective response rate(ORR),progression-free survival(PFS),and adverse reactions.The ratio difference(RD)and hazard ratio(HR)were used as the efficacy values,and the meta-analysis was performed via RevMan5.3 software.Results A total of six literatures involving 1726 patients with NSCLC were included,and 409 cases had brain metastases.Meta-analysis showed that compared with chemotherapy only or standard epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs),osimertinib was more effective in reducing the risk of disease progression(HR=0.32,95%CI:0.15-0.68,P<0.05;HR=0.48,95%CI:0.26-0.88,P<0.05).Additionally,osimertinib was more effective in improving DCR(RD=0.87,95%CI:0.82-0.91,P<0.05)and ORR(RD=0.44,95%CI:0.37-0.50,P<0.05).In terms of safety,the incidence of adverse reactions at grade 3 and above caused by osimertinib was lower than that caused by standard EGFR-TKIs or chemotherapy(RR=0.44,95%CI:0.22-0.47,P<0.05;RR=0.78,95%CI:0.62-0.97,P<0.05).Conclusion Compared with other treatment solutions,osimertinib significantly reduces the risk of brain metastasis progression,prolongs PFS,increases DCR and ORR,and has lower incidence of adverse reactions.