Detection of Plasma T790M Mutation After the First Generation EGFR-TKI Resistance of Non-Small Cell Lung Cancer in the Real World

Abstract

Background: The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has shown efficacy in mutation non-small cell lung cancer (NSCLC), but acquired resistance is inevitable. It has been confirmed that the secondary EGFR Thr790Met (T790M) mutation accounted for about 50% at acquired resistance in tumor tissue. The third generation EGFR-TKI had significantly efficacy in T790M positive NSCLC. The purpose of this study was to investigate the positive rate of plasma T790M mutation and its relationship among the clinical characteristics and the frequency of T790M mutation in acquired resistance after first line EGFR‒ TKI treatment in the real world. Method: Patients were recruited prospective from September 2017 to June 2018.The eligibility criteria of the trial included:1. Older than 18 years, histologically confirmed NSCLC stage III B/IV, EGFR mutation positive; 2. Had progressive disease (PD) after first generation EGFR-TKI by RECIST, PFS>3months; 3. excluded patients who had received the third generation TKI treatment. All patients take 10 ml of blood, and detected the T790M gene by amplification refractory mutation system (ARMS). The study was approved by the Ethics Committee of Taizhou Hospital, ethical batch number: 201637. Result: 189 patients are in the analysis (Table 1). The overall plasma T790M mutation rate was 36.51 % (69/189). The positive rate of T790M mutation after the failure of first generation EGFR-TKI treatment was not correlated with the patient's age, sex and the type of first generation TKI drugs. However, it is related to the mutation type of EGFR in baseline and the mode of progression according to Wu YL et al. reports. The frequency of T790M mutation among patients with initial exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 45.44%, 26.19% and 33.33%. The mutation rate of T790M in 19del mutant patients was higher than that of L858R mutation and other mutations (p=0.026). The frequency of T790M mutation in local progression patients was 50% after the first generation EGFR TKI was resistant to drug, when in gradual progression was 26.92%, and in dramatic progression was 38.10%. The frequency of T790M mutation of patients with local progression was significantly higher (p=0.031). Conclusion: The overall plasma T790M mutation rate was 36.51% after first generation of EGFR-TKI acquired resistance of NSCLC in the real world. The frequency of T790M mutation with initial mutation of 19 Del was higher than that of L858R mutation, and local progression was higher than gradual progression and dramatic progression.