EGFR-TKI单药与传统化疗方案治疗进展期NSCLC安全性的网状meta分析

Meta-analysis of the safety of EGFR-TKI monotherapy versus conventional chemotherapy in patients with advanced non-small cell lung cancer

目的对一至三代表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKI)与传统化疗方案治疗进展期非小细胞肺癌(NSCLC)的安全性进行比较,同时采用网状meta分析方法评价三代EGFR-TKI与一、二代之间的安全性。方法检索PubMed、Embase、Cochrane图书馆、中国生物医学文献数据库、中国知网、万方数字化期刊全文数据库、维普数据库,检索时限均为从建库至2020年12月,搜集EGFR-TKI单药对比铂类为基础培美曲塞化疗方案的随机对照试验(RCT)。筛选文献、提取资料,并用Cochrane系统评价偏倚风险评估工具对纳入研究的RCT进行偏倚风险评估,采用RevMan 5.3软件、STATA 15.1软件进行meta分析。结果meta分析结果显示,试验组(EGFR-TKI单药)、对照组(培美曲塞联合铂类)患者的腹泻[相对危险度(RR)=2.16,95%置信区间(CI)0.742~6.297,P>0.05]、便秘(RR=0.44,95%CI 0.187~1.039,P>0.05)发生率比较差异均无统计学意义。试验组白细胞减少发生率、中性粒细胞减少发生率、贫血发生率、血小板减少发生率、食欲不振发生率、恶心发生率均低于对照组(RR=0.21,95%CI 0.10~0.41,P<0.001;RR=0.21,95%CI 0.08~0.55,P<0.001;RR=0.26,95%CI 0.13~0.51,P<0.001;RR=0.39,95%CI 0.24~0.64,P<0.001;RR=0.39,95%CI 0.28~0.55,P<0.001;RR=0.30,95%CI 0.24~0.37,P<0.001);试验组皮疹发生率高于对照组(RR=9.63,95%CI 6.30~14.72,P<0.001)。对一至三代EGFR-TKI的不良反应进行网状meta分析结果显示,三代EGFR-TKI奥希替尼组白细胞减少发生率要高于一、二代EGFR-TKI,贫血发生率与埃克替尼组相似,但高于吉非替尼组和阿法替尼组(均P<0.05)。结论一至三代EGFR-TKI的血液系统、消化系统不良反应发生率均低于传统化疗方案;三代EGFR-TKI与一、二代相比,在白细胞减少及贫血发生率方面各具优势。

Objective In this study,we compared the safety of the first to third generations of epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)versus conventional chemotherapy in patients with advanced non-small cell lung cancer(NSCLC).Net-work meta-analysis was used to compare the safety among different generations of EGFR-TKIs.Methods Randomized controlled trials(RCTs)of EGFR-TKI monotherapy versus platinum-based pemetrexed chemotherapy were retrieved from PubMed,Embase,Cochrane Library,CBM,CNKI,Wanfang Database,and VIP from the establishment of the databases to December 2020.Investigators screened the literatures,extracted the information,and assessed the risk of bias for RCTs using the Cochrane Systematic Evaluation Risk of Bias Assessment Tool.The meta-analysis was performed with RevMan 5.3 software and STATA 15.1 software.Results Seven RCTs with a total of 1315 patients were included.Meta-analysis showed that there were no statistically significant differences in the incidence of diarrhea[relative risk(RR)=2.16,95%confidence interval(CI)(0.742,6.297),P>0.05]or constipation[RR=0.44,95%CI(0.187,1.039),P>0.05]between the experimental group(EGFR-TKI monotherapy group)and the control group(pemetrexed combined with platinum group).The incidences of leukopenia[RR=0.21,95%CI(0.10,0.41),P<0.001],neutropenia[RR=0.21,95%CI(0.08,0.55),P<0.001],anemia[RR=0.26,95%CI(0.13,0.51),P<0.001],thrombocytopenia[RR=0.39,95%CI(0.24,0.64),P<0.001],loss of appetite[RR=0.39,95%CI(0.28,0.55),P<0.001],and nausea[RR=0.30,95%CI(0.24,0.37),P<0.001]in the experimental group were lower than those in the control group,while the incidence of rash in the experimental group was higher than that in the control group[RR=9.63,95%CI(6.30,14.72),P<0.001].Network meta-analysis of the adverse events showed that the incidence of leukopenia in the third generation of EGFR-TKI osimertinib was higher than those in the first and second generations of EGFR-TKIs;the incidence of anemia in the osimertinib group was similar to that in the icotinib group,but was higher than those in the gefitinib and afatinib groups(both P<0.05).Conclusions Compared with traditional chemotherapy regimens,the incidence of adverse reactions in the blood and digestive systems is lower in the first to third generations of EGFR-TKIs.Compared with the first and second generations,the third-generation of EGFR-TKI has advantages in reducing the incidences of leukopenia and anemia.