Abstract 1833: De novo EGFR T790M mutation in lung cancer patients harboring sensitive EGFR mutations

Abstract

Abstract Background EGFR T790M mutation drives acquired drug resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI) in EGFR-mutant lung cancer. However, it was reported that this mutation may exist before drug exposure. This study aimed to evaluate whether the clinical outcomes are affected by the proportion of preexisting T790M mutations within a tumor. Methods We collected pretreatment tissues from 124 advanced non-small cell lung cancer patients with sensitizing EGFR mutations that were detected by direct sequencing. Genotyping for EGFR T790M was further performed using matrix-assisted laser desorption/ionization-time of flight/mass spectrometry. T790M-positive patients were divided to two subgroups according to T790M mutant signal frequency. Results The T790M mutation was found in 31 (25.0%) patients. The T790M mutation frequency at which the risk of progression to EGFR-TKI begins to increase was estimated to be 2.0%. The patients with T790M-positive tumor had shorter time to progression (TTP) after EGFR-TKI (median 6.3 months vs. 11.5 months; P < 0.001) and overall survival (OS) (median 16.1 months vs. 26.5 months; P = 0.065) than those with T790M-negative tumor. Among the T790M-positive patients, the patients with high T790M frequency (n= 9) had shorter TTP (median 2.4 months vs. 6.7 months; P = 0.009) and OS (median 9.1 months vs. 18.7 months; P = 0.018) than those with low T790M frequency (n= 22). Conclusions Preexisting EGFR T790M mutation was noted in 25% of patients with EGFR-mutant lung cancer. Patients with high T790M mutation frequency had worse clinical outcomes to EGFR-TKI than patients with low T790M mutation frequency. Citation Format: Youngjoo Lee, Geon Kook Lee, Yeon-Su Lee, Wenji Zhang. De novo EGFR T790M mutation in lung cancer patients harboring sensitive EGFR mutations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1833. doi:10.1158/1538-7445.AM2014-1833