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

Ji Yun Lee, Xu Qing, Wei Xiumin, Bai Yali, Sangah Chi, So Hyeon Bak, Ho Yun Lee, Jong Mu Sun, Se Hoon Lee, Jin Seok Ahn, Eun Kyung Cho, Dong Wan Kim, Hye Ryun Kim, Young Joo Min, Sin Ho Jung, Keunchil Park, Mao Mao, Myung Ju Ahn

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)6984-6993
Number of pages10
JournalOncotarget
Volume7
Issue number6
DOIs
StatePublished - 1 Jan 2016

Keywords

  • Droplet digital PCR
  • EGFR
  • Liquid biopsy
  • NSCLC
  • TKI treatment

Cite this

Lee, J. Y., Qing, X., Xiumin, W., Yali, B., Chi, S., Bak, S. H., Lee, H. Y., Sun, J. M., Lee, S. H., Ahn, J. S., Cho, E. K., Kim, D. W., Kim, H. R., Min, Y. J., Jung, S. H., Park, K., Mao, M., & 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