EGFR-TKI与化疗比较一线治疗晚期非小细胞肺癌有效性和安全性的系统评价

Efficacy and Safety of EGFR-TKIs versus Chemotherapy as the First Line Treatment for Patients with Advanced Non-small Cell Lung Cancer:A Systematic Review

目的系统评价表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)一线治疗晚期非小细胞肺癌患者(NSCLC)的有效性和安全性。方法计算机检索PubMed、EMbase、The Cochrane Library(2015年第1期)、CBM、CNKI、VIP和WanFang Data,搜集EGFR-TKI对比化疗药一线治疗晚期NSCLC的相关随机对照试验(RCT),检索时限均为从建库至2015年3月。由2位研究者独立筛选文献、提取资料和评价纳入研究的偏倚风险后,采用RevMan 5.2软件进行Meta分析。结果共纳入9个RCT,合计3 841例受试者。对于表皮生长因子受体(EGFR)突变阳性的患者,EGFR-TKI组在无进展生存期[HR=0.41,95%CI(0.31,0.54),P<0.000 01]、客观缓解率[RR=2.23,95%CI(1.73,2.87),P<0.000 01]和生活质量方面均优于化疗组,但在总生存期方面两组差异无统计学意义[HR=1.04,95%CI(0.88,1.24),P=0.62]。在安全性方面,EGFR-TKI组腹泻[RR=3.81,95%CI(2.15,6.76),P<0.001]和皮疹[RR=8.14,95%CI(3.55,18.68),P<0.001]的发生率明显高于化疗组,但产生的血液毒性明显低于化疗组。结论 EGFR-TKI一线治疗EGFR突变阳性的晚期NSCLC显示出明显优势,且可明显减少不良反应。受纳入研究数量和质量的限制,上述结论尚需开展更多高质量的研究予以验证。

Objective To systematically evaluate the efficacy and safety of epidermal growth factor receptortyrosine kinase inhibitors（EGFR-TKIs） as the first-line treatment for patients with advanced non-small cell lung cancer（NSCLC）.Methods Databases including PubMed,EMbase,The Cochrane Library（Issue 1,2015）,CBM,CNKI,VIP and WanFang Data were electronically searched from inception to March 2015,to collect randomized controlled trials（RCTs） about EGFR-TKIs versus chemotherapy for advanced NSCLC patients.Two reviewers independently screened literature,extracted data,and assessed the risk of bias of included studies.Then,meta-analysis was performed by RevMan5.2 software.Results A total of 9 RCTs involving 3 841 patients were included.The results of meta-analysis showed that：for patients with EGFR mutation-positive,the rate of progression-free survival（PFS）（HR=0.41,95%CI 0.31 to 0.54,P0.000 01）,objective response rate（ORR）（RR=2.23,95%CI 1.73 to 2.87,P0.000 01） and quality of life（QoL） in the EGFR-TKI group were superior to the chemotherapy group;There was no statistical difference between two groups in rate of overall survival（OS）（HR=1.04,95%CI 0.88 to 1.24,P=0.62）.The incidences of diarrhea（RR=3.81,95%CI 2.15 to 6.76,P0.001） and rash（RR=8.14,95%CI 3.55 to 18.68,P0.001） were significantly higher,but the incidence of blood toxicity was lower in the EGFR-TKI group that those in the chemotherapy group.Conclusions Current evidence shows EGFR-TKI is superior to chemotherapy for advanced NSCLC patients with EGFR mutation-positive.However,due to the limited quantity and quality of the included studies,more high-quality studies are needed to verify the above conclusion.