Clinical Study Of EGFR-TKI Combined With Bevacizumab In The Treatmwnt Of Advanced Non-small Cell Lung Cancer

Introduction: In recent years,lung malignant tumor has gradually become the malignant disease with the highest morbidity and mortality in the word,and the proportion of patients with non-small cell lung cancer(NSCLC)in the total number of lung cancer patients is also increasing year by year.Epidermal growth factor receptor(EGFR)tyrosine kinase inehibitors(TKIs)have been established as the standard therapy in the first-line treatment of advanced NSCLC with EGFR mutations,but the efficacy can still be improved by combination therapy.However,there are no real-world data reported about A+T,the influencing factors of PFS cannot be determined,and there is limited information about the acquired resistance mutations in patients treated with the the regimen.This article is a real-world study to evaluate the clinical efficacy and acquired drug resistance mutation of bevacizumab combined with EGFR-TKI compared with EGFR-TKI monotherapy in the treatment of advanced non-small cell lung cancer patients with EGFR sensitive mutations by retrospective analysis,aiming to providecertain theoretical basis for the further clinical application of subsequent A+T combination therapy.Object: We aimed to investigate the clinical efficacy of EGFR tyrosine kinase inhibitor(TKI,T)plus bevacizumab(an antiangiogenic therapy,trade name Avastin,A)and the first generation of EGFR-TKI alone were used to treat patients with advanced EGFR sensitive mutation of non-small cell lung cancer,to study its clinical efficacy in the real population and explore its acquired drug resistance mutation.Methods: This study included 256 NSCLC patients harboring EGFR sensitizing mutations(EGFR 19 del and L858R)who underwent nextgeneration sequencing(NGS)with 168-gene panel prior to treatment between Jan 2015 to Aug 2018.After screening by PS Match(cut-off value is 0.01),A total of 180 patients were enrolled in this study,including 60 patients in A+T treatment group.120 patients in EGFR-TKI monotherapy group were identified after propensity score matching(Ratio of 1: 2).The adverse reactions,therapeutic effects and acquired drug resistance mutation of the two groups of patients were summarized and analyzed.The primary observation endpoint of this study is median progression-free survival(PFS)and potential acquired drug resistance mutation,while the secondary observation endpoint is median overall survival(OS).Results: Baseline clinical characteristics were not significantlydifferent between the two groups at baseline.Compared with EGFR-TKI treatment group alone,the overall response rate(ORR)of the A+T treatment group is higher(95 % vs 74.2 % %,p = 0.001),and longer median progression-free survival(PFS,16.5m vs 12.0m,HR=0.7,p=0.001).Until Jan 2019,31 patients in the A+T treatment group and103 patients in the TKI treatment group with disease progression were evaluated respectively,and tissue biopsies and NGS analysis of 168 genomes were performed respectively.The study found that EGFR T790 M mutation is the main acquired drug resistance mutation after treatment and disease progression in the TKI treatment group alone,which can be detected in 51.5%(53/103)of patients with disease progression,followed by EGFR amplification(15.5%,16/103)and MET amplification(6.8%,7/103),respectively.On the contrary,T790 M mutation rate in A+T treatment group was significantly lower(35.5%,11/31,p=0.0003).Conclusion: 1.The combination of A + T on the first-line can significantly improve the PFS and ORR of NSCLC patients with EGFR sensitive mutations;2.There was no serious adverse reaction in the A + T combination treatment group,and its safety was not worse than that of TKI treatment alone;3.Among patients with acquired drug resistance,the EGFR T790 Mmutation in the A + T combination treatment group was lower than that in the TKI treatment group alone.