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Longitudinal monitoring of EGFR mutations in plasma predicts outcomes of NSCLC patients treated with EGFR TKIs: Korean Lung Cancer Consortium (KLCC-12-02).

Publication ,  Journal Article
Lee, JY; Qing, X; Xiumin, W; Yali, B; Chi, S; Bak, SH; Lee, HY; Sun, J-M; Lee, S-H; Ahn, JS; Cho, EK; Kim, D-W; Kim, HR; Min, YJ; Jung, S-H ...
Published in: Oncotarget
February 9, 2016

We hypothesized that plasma-based EGFR mutation analysis for NSCLC may be feasible for monitoring treatment response to EGFR TKIs and also predict drug resistance.Clinically relevant mutations including exon 19 deletion (ex19del), L858R and T790M were analyzed using droplet digital PCR (ddPCR) in longitudinally collected plasma samples (n = 367) from 81 NSCLC patients treated with EGFR TKI. Of a total 58 baseline cell-free DNA (cfDNA) samples available for ddPCR analysis, 43 (74.1%) had the same mutation in the matched tumors (clinical sensitivity: 70.8% [17/24] for L858R and 76.5% [26/34] for ex19del). The concordance rates of plasma with tissue-based results of EGFR mutations were 87.9% for L858R and 86.2% for ex19del. All 40 patients who were detected EGFR mutations at baseline showed a dramatic decrease of mutant copies (>50%) in plasma during the first two months after treatment. Median progression-free survival (PFS) was 10.1 months for patients with undetectable EGFR v 6.3 months for detectable EGFR mutations in blood after two-month treatment (HR 3.88, 95% CI 1.48-10.19, P = 0.006). We observed emerging resistance with early detection of T790M as a secondary mutation in 14 (28.6%) of 49 patients. Plasma-based EGFR mutation analysis using ddPCR can monitor treatment response to EGFR TKIs and can lead to early detection of EGFR TKIs resistance. Further studies confirming clinical implications of EGFR mutation in plasma are warranted to guide optimal therapeutic strategies upon knowledge of treatment response and resistance.

Duke Scholars

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Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

February 9, 2016

Volume

7

Issue

6

Start / End Page

6984 / 6993

Location

United States

Related Subject Headings

  • Survival Rate
  • Republic of Korea
  • Real-Time Polymerase Chain Reaction
  • Protein Kinase Inhibitors
  • Prospective Studies
  • Prognosis
  • Neoplasm Staging
  • Neoplasm Grading
  • Mutation
  • Middle Aged
 

Citation

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Lee, J. Y., Qing, X., Xiumin, W., Yali, B., Chi, S., Bak, S. H., … Ahn, M.-J. (2016). Longitudinal monitoring of EGFR mutations in plasma predicts outcomes of NSCLC patients treated with EGFR TKIs: Korean Lung Cancer Consortium (KLCC-12-02). Oncotarget, 7(6), 6984–6993. https://doi.org/10.18632/oncotarget.6874
Lee, Ji Yun, Xu Qing, Wei Xiumin, Bai Yali, Sangah Chi, So Hyeon Bak, Ho Yun Lee, et al. “Longitudinal monitoring of EGFR mutations in plasma predicts outcomes of NSCLC patients treated with EGFR TKIs: Korean Lung Cancer Consortium (KLCC-12-02).Oncotarget 7, no. 6 (February 9, 2016): 6984–93. https://doi.org/10.18632/oncotarget.6874.
Lee, Ji Yun, et al. “Longitudinal monitoring of EGFR mutations in plasma predicts outcomes of NSCLC patients treated with EGFR TKIs: Korean Lung Cancer Consortium (KLCC-12-02).Oncotarget, vol. 7, no. 6, Feb. 2016, pp. 6984–93. Pubmed, doi:10.18632/oncotarget.6874.
Lee JY, Qing X, Xiumin W, Yali B, Chi S, Bak SH, Lee HY, Sun J-M, Lee S-H, Ahn JS, Cho EK, Kim D-W, Kim HR, Min YJ, Jung S-H, Park K, Mao M, Ahn M-J. Longitudinal monitoring of EGFR mutations in plasma predicts outcomes of NSCLC patients treated with EGFR TKIs: Korean Lung Cancer Consortium (KLCC-12-02). Oncotarget. 2016 Feb 9;7(6):6984–6993.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

February 9, 2016

Volume

7

Issue

6

Start / End Page

6984 / 6993

Location

United States

Related Subject Headings

  • Survival Rate
  • Republic of Korea
  • Real-Time Polymerase Chain Reaction
  • Protein Kinase Inhibitors
  • Prospective Studies
  • Prognosis
  • Neoplasm Staging
  • Neoplasm Grading
  • Mutation
  • Middle Aged