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EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: analysis of LUX-Lung 3 and 6
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EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: analysis of LUX-Lung 3 and 6
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Journal Article
EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: analysis of LUX-Lung 3 and 6
2017
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Adenocarcinoma - drug therapy
/ Adult
/ Afatinib
/ Aged
/ Antineoplastic Combined Chemotherapy Protocols - therapeutic use
/ Biomedical and Life Sciences
/ Biopsy
/ Blood Chemical Analysis - methods
/ DNA Mutational Analysis - methods
/ Female
/ Humans
/ Kinases
/ Lung Neoplasms - drug therapy
/ Male
/ Mutation
/ Oncology
/ Patients
/ Plasma
/ Quinazolines - administration & dosage
/ Tumors
