Plasma EGFR T790M ctDNA status is associated with clinical outcome in advanced NSCLC patients with acquired EGFR-TKI resistance

• Published in: Scientific reports Vol. 6; no. 1; p. 20913
• Main Authors: Zheng, D., Ye, X., Zhang, M. Z., Sun, Y., Wang, J. Y., Ni, J., Zhang, H. P., Zhang, L., Luo, J., Zhang, J., Tang, L., Su, B., Chen, G., Zhu, G., Gu, Y., Xu, J. F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.02.2016; Nature Publishing Group
• Subjects: 49/23; 692/4028/67/1612/1350; 692/4028/67/1857; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Disease Progression; DNA, Neoplasm - blood; Drug Resistance, Neoplasm - drug effects; Epidermal growth factor receptors; Feasibility studies; Female; Humanities and Social Sciences; Humans; Invasiveness; Lung cancer; Lung Neoplasms - blood; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Middle Aged; multidisciplinary; Mutation; Mutation - genetics; Neoplasm Staging; Neoplastic Cells, Circulating - metabolism; Non-small cell lung carcinoma; Plasma; Polymerase Chain Reaction; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Receptor, Epidermal Growth Factor - blood; Receptor, Epidermal Growth Factor - genetics; Reproducibility of Results; Science; Science (multidisciplinary); Survival Analysis; Treatment Outcome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep20913

EGFR T790M mutation occurs in half of non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI (TKI) resistance, based on tumor re-biopsies using an invasive clinical procedure. Here, we dynamically monitored T790M mutation in circulating tumor DNA (ctDNA) using serial plasma samples from NSCLC patients receiving TKI through Droplet Digital PCR (ddPCR) method and the associations between overall survival (OS) starting from initial TKI treatment and the T790M ctDNA status detected in plasma were analyzed. Among 318 patients, 117 who acquired TKI resistance were eligible for the analysis. T790M ctDNA was detected in the plasma of 55/117 (47%) patients. Almost half of the T790M ctDNA positive patients were identified at a median time of 2.2 months prior to clinically progressive disease (PD). Furthermore, within the patients receiving TKI treatment at 2 nd line or later, the T790M ctDNA positive group had significantly shorter OS than the negative group (median OS: 26.9 months versus NA, P = 0.0489). Our study demonstrates the feasibility of monitoring EGFR mutation dynamics in serial plasma samples from NSCLC patients receiving TKI therapy. T790M ctDNA can be detected in plasma before and after PD as a poor prognostic factor.