P3.02b-098 Plasma T790M Mutation Associates with Extensive Progression in Non-small Cell Lung Cancer with Acquired Resistance to EGFR Inhibitors: Topic: EGFR RES

Abstract

T790M mutation is a major mechanism for clinical failure in non-small cell lung cancer (NSCLC) patients with EGFR-TKI therapy. Acknowledgement of its frequency/abundance and its correlation with clinical characteristics will be of significant importance for the management of those patients in clinical practice and future trial design. Due to the difficulty of rebiopsy, plasma ctDNA is an ideal biopsy for detection of T790M mutation. 314 patients with advanced or recurrent NSCLC who had progressed during EGFR-TKIs treatment were enrolled prospectively. T790M mutation was determined in plasma samples by ARMS and ddPCR assay. Disease failure site was defined into three types of chest limited (CP), brain limited (BP) and extensive progression (EP). The T790M mutation status was analyzed for their correlations with failure site and clinical characteristics. T790M mutations were detected in 30.9% and 46.8% of the patients by ARMS and ddPCR. The concordance rate was 78.3% between two methods. Compared to patients with CP and BP, EP patients showed significant higher rate for T790M+ determined by both ARMS and ddPCR (73.8% and 54.7%, p<0.001). In T790M positive population, the median T790M abundance was 1.2% (range, 0.04%-70.3%), and the median abundance of CP, BP, and EP was 0.66%, 1.52%, and 2.61%, respectively (p＝0.062). When adjusting for TKI response, worse PFS was found correlated with the plasma T790M mutation by ddPCR. Plasma T790M status correlates the extensive progression in NSCLC patients with EGFR-TKI therapy, which may provide the important ancillary information for treatment decision-making.