The Impact Of Cocurrent Alterations On EGFR-TKIs Efficacy And Progression Patterns After Drug Resistance In Advanced EGFR-mutant NSCLC Patients

Objective: Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improved survival and quality of life in EGFR-mutant non-small cell lung cancer(NSCLC)patients.However,many patients show primary/early resistance.In addition,patients who initially respond to EGFR-TKIs show various clinical outcomes.Previous studies have shown that EGFR concurrent alterations can affect the efficacy of EGFR-TKIs.The study aims to analyze the characteristics of concurrent alterations in advanced EGFR-mutant NSCLC patients who were treated with EGFR-TKIs,and to evaluate the influence of different concurrent alterations on the efficacy of EGFR-TKIs and the pattern of disease progression.Methods: In this retrospective study,we enrolled advanced NSCLC patients who underwent polygenetic testing,harboured EGFR mutaions and treated with EGFR-TKIs at the Cancer Center of Shengjing Hospital of China Medical University from January2012 to June 2019.The general clinicopathological data,genetic test data and clinical outcome data of these patients were collected.SPSS software 23.0 was used for statistical analysis.Fisher’s exact probability method,Log-rank test and Kaplan-Meier method were used to analyze the prevalence and distribution characteristics of specific concurrent alteration,the relationship between specific concurrent alteration and the clinical outcomes of EGFR-TKIs treatment,and the effect of concurrent alterations on the progression pattern after EGFR-TKIs resistance.Results: A total of 18 EGFR-mutant pre-treatment samples were collected,the most frequent concurrent alterations were in TP53(66.7%),PTEN(33.3%),intra-EGFR(27.8%),ROS1(22.2%),ATRX(22.2%),KMT2C(22.2%),PDGFRA(22.2%)and PAX5(22.2%).Patients with concurrent intra-EGFR alterations showed a tendency of longer progression-free survival(PFS)and overall survival(OS)(PFS: 8.7 vs 7.8,p=0.948;OS: NR vs 22.5,p=0.669),while concurrent TP53 and PTEN alterations tended to have shorter PFS and OS(TP53: PFS: 6.4 vs 8.7,p=0.629;OS: 16.8 vs 22.5,p=0.21;PTEN: PFS: 6.4 vs 8.9,p=0.464;OS: 22.5 vs NR,p=0.624).However,these differences were not significant.No correlation was found between primary resistance,patterns of progression and specific concurrent alterations.Conclusion: Concurrent alterations are widely exist in EGFR-mutant pre-treatment NSCLC patients and are associated with efficacy and clinical outcomes of EGFR-TKIs.No correlation was found between specific concurrent alterations and the primary resistance and progression patterns of EGFR-TKIs.Studies in larger populations are needed.