贝伐单抗联合化疗治疗非小细胞肺癌的meta分析

Bevacizumab Combined with Chemotherapy for Advanced Non-small Cell Lung Cancer: A meta-analysis

背景与目的贝伐单抗是抑制血管内皮生长因子受体(vascular endothelial growth factor receptor,VEG-FR)的重组人源化单克隆抗体,本研究旨在系统评价贝伐单抗联合化疗治疗非小细胞肺癌(non-small cell lung cancer,NSCLC)疗效及安全性。方法计算机检索中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)、维普数据库(VIP)、万方数据库、TheCochraneLibrary、PubMed、Ovid、EMBASE及SCI等数据库,收集有关贝伐单抗联合化疗治疗NSCLC的随机对照试验(randomized control trial,RCT);主要结局指标包括有效率、无进展生存时间(progression free survival,PFS)、总生存期(overallsurvival,OS)、治疗相关死亡率及毒性反应;采用相对危险度(relative risk,RR)和风险比(hazard ratios,HR)为效应量,各效应量以95%置信区间(95%CI)表示,Stata12.0统计软件进行meta分析。结果共纳入6项RCT,共2,338例晚期NSCLC患者,meta分析结果显示,与单纯化疗方案比较,贝伐单抗(7.5mg/kg或15mg/kg)联合化疗方案可提高晚期NSCLC的有效率(RR=1.68,P<0.01,95%CI:1.31-2.15;RR=1.79,P<0.01,95%CI:1.53-2.08),降低疾病进展风险(HR=0.75,P<0.01,95%CI:0.61-0.89;HR=0.69,P<0.01,95%CI:0.62-0.77)和疾病死亡风险(HR=0.94,P<0.01,95%CI:0.77-1.10;HR=0.87,P<0.01,95%CI:0.78-0.97);高剂量贝伐单抗(15mg/kg)联合化疗方案增加了晚期NSCLC患者的治疗相关死亡率(RR=1.88,P=0.01,95%CI:1.16-3.05)及其它毒性反应的发生率。结论无论一线还是二线治疗,贝伐单抗联合化疗方案可提高晚期NSCLC患者的有效率、PFS及OS。

Background and objective Bevacizumab is a recombinant, humanised, monoclonal antibody against the vascular endothelial growth factor receptor （VEGFR）, the aim of this meta-analysis is to evaluate the clinical efficacy andsafety of bevacizumab combined with chemotherapy for non-small cell lung cancer （NSCLC）. Methods The CBM, CNKI, VIP, WanFang, The Cochrane Library, PubMed, Ovid, EMBASE and SCI etc were retrieved by computer, the randomized con-trolled trials （randomized control trial, RCT） ofbevacizumab combined with chemotherapy in the treatment of NSCLC were collected by us. The outcomes included overall survival （OS）, progression-free survival （PFS）, response rate （RR）, toxicitiesand treatment related mortality. Relative risk （RR） and hazard ratios （HR） were used for the meta-analysis and were expressed with 95% confidence intervals （95%CI）, and the software Stata 12.0 was used for meta-analyses. Results Six trials and 2,338advanced NSCLC patients were included. Meta analysis indicated that compared with chemotherapy alone, the bevacizumab （7.5 mg/kg or 15 mg/kg） combination with chemotherapy could increase overall survival rate （RR=1.68, P〈0.01, 9S%CI：1.31-2.15; RR= 1.79, P〈0.01, 95%CI： 1,53-2.08）, and could decrease the progression of the disease risk （HR=0.75, P〈0.01,95%CI： 0.61-0.89; HR=0.69, P〈0.01, 95%CI： 0.62-0.77） and the risk of disease death （HR=0.94, P〈0.01, 95%CI： 0.77-1.10; HR=0.87, P〈0.01, 95%CI： 0.78-0.97）. The high dose of bevacizumab （15 mg/kg） combination with chemotherapy couldincrease the treatment related mortality （RR=l.88, P=0.010, 95%CI： 1.16-3.05） and the rates of other toxic reaction. Conclu- sion Whether first-line or second-line treatment, the addition of bevacizumab to chemotherapy in patients with advancedNSCLC prolongs RR, OS and PFS.