EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: Analysis of LUX-Lung 3 and 6
Journal
British Journal of Cancer
Journal Volume
116
Journal Issue
2
Pages
175-185
Date Issued
2017
Author(s)
Wu Y.-L
Sequist L.V
Hu C.-P
Feng J
Lu S
Huang Y
Li W
Hou M
Schuler M
Mok T
Yamamoto N
O'Byrne K
Hirsh V
Gibson N
Massey D
Kim M
Abstract
Background:In the Phase III LUX-Lung 3/6 (LL3/LL6) trials in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma patients, we evaluated feasibility of EGFR mutation detection using circulating cell-free DNA (cfDNA) and prognostic and predictive utility of cfDNA positivity (cfDNA+).Methods:Paired tumour and blood samples were prospectively collected from randomised patients. Mutations were detected using cfDNA from serum (LL3) or plasma (LL6) by a validated allele-specific quantitative real-Time PCR kit.Results:EGFR mutation detection rates in cfDNA were 28.6% (serum) and 60.5% (plasma). Mutation detection in blood was associated with advanced disease characteristics, including higher performance score, number of metastatic sites and bone/liver metastases, and poorer prognosis. In patients with common EGFR mutations, afatinib improved progression-free survival vs chemotherapy in cfDNA+ (LL3: HR, 0.35; P=0.0009; LL6: HR, 0.25; P<0.0001) and cfDNA-(LL3: HR, 0.46; P<0.0001; LL6: HR, 0.12; P<0.0001) cohorts. A trend towards overall survival benefit with afatinib was observed in cfDNA+ patients.Conclusions:Plasma cfDNA is a promising alternative to biopsy for EGFR testing. Detectable mutation in blood was associated with more advanced disease and poorer prognosis. Afatinib improved outcomes in EGFR mutation-positive patients regardless of blood mutation status. ? The Author(s) named above.
Subjects
afatinib; circulating cell-free DNA; EGFR mutation; ERBB family blocker; non-small cell lung cancer
Other Subjects
afatinib; cisplatin; DNA; epidermal growth factor receptor; gemcitabine; pemetrexed; afatinib; antineoplastic agent; DNA; EGFR protein, human; epidermal growth factor receptor; quinazoline derivative; adult; aged; allele; Article; blood sampling; bone metastasis; cancer combination chemotherapy; cancer patient; cancer prognosis; cancer survival; clinical evaluation; controlled study; female; human; liver metastasis; lung adenocarcinoma; major clinical study; male; multiple cycle treatment; outcome assessment; overall survival; phase 3 clinical trial; priority journal; progression free survival; randomized controlled trial; real time polymerase chain reaction; adenocarcinoma; blood; blood analysis; clinical trial; dna mutational analysis; feasibility study; genetics; Lung Neoplasms; middle aged; mortality; multicenter study; predictive value; procedures; prognosis; very elderly; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Blood Chemical Analysis; DNA Mutational Analysis; DNA, Neoplasm; Feasibility Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Predictive Value of Tests; Prognosis; Quinazolines; Receptor, Epidermal Growth Factor
Publisher
Nature Publishing Group
Type
journal article