Meta-analysis Of EGFR-TKIs Combined With Anti-vascular Targeting Drugs Versus EGFR-TKIs In The Treatment Of Advanced Non-small Cell Lung Cancer

Objective: In this study,meta analysis was used to compare the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors combined with anti-vascular targeting drugs and EGFR-TKIs in patients with advanced non-small cell lung cancer(NSCLC).Methods: Search for English databases such as Pub Med,EMBASE and The Cochrane Library,as well as Chinese databases such as CBM,Wanfang,Weipu,and other related meetings like ASCO.EGFR-TKIs combined with anti-vascular targeting drugs were collected to compare EGFR-TKIs with EGFR-TKIs in the treatment of advanced NSCLC patients:a randomized controlled trial(RCT).According to the Cochrane systematic review method,the objective response rate(ORR),disease control rate(DCR),progression free survival(PFS),overall survival(overall survival,OS)and adverse effect(AE)were analyzed by Review Manager5.3.0 software.Also the Sensitivity analysis,subgroup analysis and bias analysis were carried out.Results: A total of 7 studies involving 2313 patients were included in the meta-analysis.The experimental group was EGFR-TKIs combined with anti-vascular targeting drugs,and the control group was EGFR-TKIs or combined with placebo.The results showed that EGFR-TKIs combined with anti-vascular targeting drugs significantly increased PFS in patients compared with EGFR-TKIs(HR=0.63,95%CI: [0.51,0.79],P<0.0001),ORR(RR=1.40).,95% CI: 1.15,1.72,P = 0.0009),DCR(RR = 1.28,95% CI: [1.08,1.52],P = 0.005),the difference was statistically significant.The OS difference was not statistically significant(HR=0.91,95% CI:[0.83,1.01],P=0.07).In the subgroup analysis,combination therapy also significantly improved ORR and PFS in patients with unexplained EGFR mutations after failure of first-line or second-line chemotherapy.Combination therapy significantly increased ≥3 diarrhea(15.3% vs 3.1%,P<0.00001),rash(14.3% vs8.5%,P<0.00001),hypertension(6.8% vs 1.5%,P<0.00001)and AE was discontinued(15.99% vs 8.19%,P < 0.00001);there was no significant difference in the incidence of bleeding events(2.6% vs 1.3%,P = 0.06).Conclusion: EGFR-TKIs combined with anti-vascular targeting drugs significantly increased efficacy in patients with advanced NSCLC compared with EGFR-TKIs.But the OS did not increase significantly.The incidence of serious adverse reactions and discontinuation of treatment due to adverse reactions is also high.Therefore,more large-scale and high-quality clinical trials should be conducted to explore the efficacy of combination beneficiary population,treatment timing and treatment strategy in the future.