Meta-analysis of the safety of EGFR-TKI monotherapy versus conventional chemotherapy in patients with advanced non-small cell lung cancer
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 1 315 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.
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