Retrospective Study Of Advanced NSCLC Chinese Patients With EGFR Mutation-positive Treated With Osimertinib

Objective:The purpose of our study was to retrospectively analyze the genetic mutations,clinical features,and therapeutic effects of Ossertinib-treated EGFR mutation-positive patients with advanced NSCLC in the real world,to clarify the importance of genetic testing in targeted therapy,explore the resistance mechanism of Osimertinib,and find the dominant population suitable for drug use,in order to provide evidence for clinical decision-making.Materials and Methods:We retrospectively analyzed the clinical data and EGFR mutations in 111 patients with advanced NSCLC treated with Osimertinib at the Chinese PLA General Hospital from March 2015 to November 2018.Molecular diagnostic methods in this study is second generation sequencing.RESULTS:1.111 patients had complete case report data for efficacy analysis.The patients selected in this study were all EGFR-positive mutations and had at least one genetic test.The overall objective response rate(ORR)was 63.1%,and 70 patients achieved partial or complete remission.The disease control rate was 82.9%(90/111)and the median progression-free survival(PFS)was 12.2 months(95%CI 9.7-14.7 months).A total of 41(36.9%)patients died,with a median overall survival(OS)of 29.5 months(95%CI 27.0-32.0 months).2.Some complex mutations were found in reanalysis after osimertinib resistance,including the TP53 mutations(usually with other mutations);C797Smutations;MET amplification;EGFR amplification;KRAS or PIK3CA mutation;SCLC conversion;B-cell lymphoma 2(BCL-2)Sample 11(BIM)deletion polymorphism and ALK rearrangement.The PFS for patients with the T790M mutation(n=41)was significantly longer than those with the T790M mutation harboring the abovementioned complex mutations(n=13)(16.7 m vs.10.8 m,P= 0.0075).Patients with a single EGFR mutation(n=87)had a longer PFS than those with an EGFR mutation harboring these complex mutations(n=24)(14.63 m vs.6.63 m,P=0.0001).These complex mutations may be the mechanism of Osimertinib resistance.3.Patients treated with first-generation TKI for more than 10.1 months had a significant prolongation of PFS with sequential Osimertinib treatment(16.4 months vs.7.1 months p=0.0035).4.No smoking history and PS<2 were independent predictors of PFS in patients treated with Osimertinib,with or without brain,bone or liver metastases.Conclusion:This study confirmed the mechanism of Osimertinib resistance from a clinical perspective,and demonstrated the importance of tissue gene detection and dynamic gene detection during targeted therapy.It proved that obtaining a longer PFS after treatment with first-generation TKI is a predictor of Osimertinib treatment.It confirmed the history of no smoking,PS<2 were the dominant population for Osimertinib treatment;provides a clinical basis for Osimertinib treatment of advanced NSCLC Chinese patients with positive EGFR mutations.