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06.11.2019 | Original Research Article

Dynamics of Plasma EGFR T790M Mutation in Advanced NSCLC: A Multicenter Study

verfasst von: Zhengquan Yang, Jialu Li, Yujie Hu, Meihua Chen, Danli Peng, Dan Zong, Qingjuan Shang, Lianqin Tao, Yanling Zhao, Yiyun Ni, Jinyan Ye, Yupeng Xie, Li Yang, Quan Lin, Chang Cai, Ning Xu, Xiaoping Huang, Xiaoting Dong, Zhonghui Zhou, Yali Yu, Zongxiao Shangguan, Yangyang Xu, Weiping Ying, Meiling Weng, Zuguo Yuan, Zhijun Dong, Jifa Li, Zhe Zheng, Jiongwei Pan, Lu Liu, Junhui Ye, Zhan Zhang, Wenfeng Li, Junfei Zhu, Shengnan Jin, Yuping Li, Chunming Ding

Erschienen in: Targeted Oncology | Ausgabe 6/2019

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Abstract

Background

Droplet digital polymerase chain reaction (ddPCR) is an emerging technology for quantitative cell-free DNA oncology applications. However, a ddPCR assay for the epidermal growth factor receptor (EGFR) p.Thr790Met (T790M) mutation suitable for clinical use remains to be established with analytical and clinical validations.

Objective

We aimed to develop and validate a new ddPCR assay to quantify the T790M mutation in plasma for monitoring and predicting the progression of advanced non-small-cell lung cancer (NSCLC).

Methods

Specificity of the ddPCR assay was evaluated with genomic DNA samples from healthy individuals. The inter- and intraday variations of the assay were evaluated using mixtures of plasmid DNA containing wild-type EGFR and T790M mutation sequences. We assessed the clinical utility of the T790M assay in a multicenter prospective study in patients with advanced NSCLC receiving tyrosine kinase inhibitor (TKI) treatment by analyzing longitudinal plasma DNA samples.

Results

We set the criteria for a positive call when the following conditions were satisfied: (1) T790M mutation frequency > 0.098% (3 standard deviations above the background signal); (2) at least two positive droplets in duplicate ddPCR reactions. Among the 62 patients with advanced NSCLC exhibiting resistance to TKI treatment, 15 had one or more serial plasma samples that tested positive for T790M. T790M mutation was detected in the plasma as early as 205 days (median 95 days) before disease progression, determined by imaging analysis. Plasma T790M concentrations also correlated with intervention after disease progression.

Conclusions

We developed a ddPCR assay to quantify the T790M mutation in plasma. Quantification of longitudinal plasma T790M mutation may allow noninvasive assessment of drug resistance and guide follow-up treatment in TKI-treated patients with NSCLC.

Trial Registration

Clinical Trials.gov identifier: NCT02804100.

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Titel: Dynamics of Plasma EGFR T790M Mutation in Advanced NSCLC: A Multicenter Study
verfasst von: Zhengquan Yang
Jialu Li
Yujie Hu
Meihua Chen
Danli Peng
Dan Zong
Qingjuan Shang
Lianqin Tao
Yanling Zhao
Yiyun Ni
Jinyan Ye
Yupeng Xie
Li Yang
Quan Lin
Chang Cai
Ning Xu
Xiaoping Huang
Xiaoting Dong
Zhonghui Zhou
Yali Yu
Zongxiao Shangguan
Yangyang Xu
Weiping Ying
Meiling Weng
Zuguo Yuan
Zhijun Dong
Jifa Li
Zhe Zheng
Jiongwei Pan
Lu Liu
Junhui Ye
Zhan Zhang
Wenfeng Li
Junfei Zhu
Shengnan Jin
Yuping Li
Chunming Ding
Publikationsdatum: 06.11.2019
Verlag: Springer International Publishing
Erschienen in: Targeted Oncology / Ausgabe 6/2019
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-019-00682-0

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Dynamics of Plasma EGFR T790M Mutation in Advanced NSCLC: A Multicenter Study