title: Plasma EGFR T790M ctDNA status is associated with clinical outcome in advanced NSCLC patients with acquired EGFR-TKI resistance.
abstract: 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.
authors: Shanghai Pulmonary Hospital, Tongji University Medical School, Shanghai, China.
authors: D
authors: D
authors: Zheng
authors: Asia &Emerging Markets Innovative Medicine, AstraZeneca R&D, Shanghai, China.
authors: X
authors: X
authors: Ye
authors: Research and Development Information, AstraZeneca, Shanghai, China.
authors: M Z
authors: MZ
authors: Zhang
authors: Asia &Emerging Markets Innovative Medicine, AstraZeneca R&D, Shanghai, China.
authors: Y
authors: Y
authors: Sun
authors: Shanghai Pulmonary Hospital, Tongji University Medical School, Shanghai, China.
authors: J Y
authors: JY
authors: Wang
authors: Shanghai Pulmonary Hospital, Tongji University Medical School, Shanghai, China.
authors: J
authors: J
authors: Ni
authors: Shanghai Pulmonary Hospital, Tongji University Medical School, Shanghai, China.
authors: H P
authors: HP
authors: Zhang
authors: Shanghai Pulmonary Hospital, Tongji University Medical School, Shanghai, China.
authors: L
authors: L
authors: Zhang
authors: Shanghai Pulmonary Hospital, Tongji University Medical School, Shanghai, China.
authors: J
authors: J
authors: Luo
authors: Shanghai Pulmonary Hospital, Tongji University Medical School, Shanghai, China.
authors: J
authors: J
authors: Zhang
authors: Shanghai Pulmonary Hospital, Tongji University Medical School, Shanghai, China.
authors: L
authors: L
authors: Tang
authors: Shanghai Pulmonary Hospital, Tongji University Medical School, Shanghai, China.
authors: B
authors: B
authors: Su
authors: Shanghai Pulmonary Hospital, Tongji University Medical School, Shanghai, China.
authors: G
authors: G
authors: Chen
authors: Asia &Emerging Markets Innovative Medicine, AstraZeneca R&D, Shanghai, China.
authors: G
authors: G
authors: Zhu
authors: Asia &Emerging Markets Innovative Medicine, AstraZeneca R&D, Shanghai, China.
authors: Y
authors: Y
authors: Gu
authors: Shanghai Pulmonary Hospital, Tongji University Medical School, Shanghai, China.
authors: J F
authors: JF
authors: Xu
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D004273:DNA, Neoplasm / Q000097:blood*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D066246:ErbB Receptors / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D016133:Polymerase Chain Reaction; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015203:Reproducibility of Results; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors