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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)

Oncotarget, 2016-02, Vol.7 (6), p.6984-6993

Copyright: © 2016 Lee et al. 2016 ;ISSN: 1949-2553 ;EISSN: 1949-2553 ;DOI: 10.18632/oncotarget.6874 ;PMID: 26755650

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Title:
Longitudinal monitoring of EGFR mutations in plasma predicts outcomes of NSCLC patients treated with EGFR TKIs: Korean Lung Cancer Consortium (KLCC-12-02)
Author: Lee, Ji Yun ; Qing, Xu ; Xiumin, Wei ; Yali, Bai ; Chi, Sangah ; Bak, So Hyeon ; Lee, Ho Yun ; Sun, Jong-Mu ; Lee, Se-Hoon ; Ahn, Jin Seok ; Cho, Eun Kyung ; Kim, Dong-Wan ; Kim, Hye Ryun ; Min, Young Joo ; Jung, Sin-Ho ; Park, Keunchil ; Mao, Mao ; Ahn, Myung-Ju
Subjects: Adenocarcinoma - blood ; Adenocarcinoma - drug therapy ; Adenocarcinoma - genetics ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor - blood ; Biomarkers, Tumor - genetics ; Carcinoma, Adenosquamous - blood ; Carcinoma, Adenosquamous - drug therapy ; Carcinoma, Adenosquamous - genetics ; Carcinoma, Non-Small-Cell Lung - blood ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Squamous Cell - blood ; Carcinoma, Squamous Cell - drug therapy ; Carcinoma, Squamous Cell - genetics ; DNA Mutational Analysis ; Drug Resistance, Neoplasm - genetics ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Humans ; Longitudinal Studies ; Lung Neoplasms - blood ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Male ; Middle Aged ; Mutation - genetics ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Protein Kinase Inhibitors - therapeutic use ; Real-Time Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor - blood ; Receptor, Epidermal Growth Factor - genetics ; Republic of Korea ; Research Paper ; Survival Rate
Is Part Of: Oncotarget, 2016-02, Vol.7 (6), p.6984-6993
Description: 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.
Publisher: United States: Impact Journals LLC
Language: English
Identifier: ISSN: 1949-2553
EISSN: 1949-2553
DOI: 10.18632/oncotarget.6874
PMID: 26755650
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central
Alma/SFX Local Collection

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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)

Copyright: © 2016 Lee et al. 2016 ;ISSN: 1949-2553 ;EISSN: 1949-2553 ;DOI: 10.18632/oncotarget.6874 ;PMID: 26755650

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