Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0123587
Title: Impact of smoking and brain metastasis on outcomes of advanced EGFR mutation lung adenocarcinoma patients treated with first line epidermal growth factor receptor tyrosine kinase inhibitors
Authors: Jain A.
Lim C. 
Gan E.M.
Ng D.Z.
Ng Q.S.
Ang M.K. 
Takano A. 
Chan K.S. 
Tan W.M.
Kanesvaran R. 
Toh C.K. 
Loo C.M. 
Hsu A.A.L. 
Devanand A. 
Lim C.H. 
Koong H.N. 
Koh T. 
Fong K.W. 
Yap S.P.
Kim S.W.
Chowbay B. 
Oon L. 
Lim K.H. 
Lim W.T. 
Tan E.H. 
Tan D.S.W. 
Keywords: afatinib
erlotinib
gefitinib
vasculotropin
epidermal growth factor receptor
protein kinase inhibitor
advanced cancer
age
aged
Article
Asia
brain metastasis
cancer palliative therapy
cancer staging
cancer survival
cohort analysis
controlled study
correlational study
disease association
EGFR gene
female
follow up
human
lung adenocarcinoma
major clinical study
male
overall survival
progression free survival
retrospective study
sex difference
smoking
treatment outcome
adenocarcinoma
adult
adverse effects
antagonists and inhibitors
brain tumor
demography
disease course
disease free survival
dna mutational analysis
drug effects
enzymology
genetics
Kaplan Meier method
Lung Neoplasms
middle aged
multivariate analysis
mutation
reflex
secondary
smoking
treatment outcome
very elderly
Adenocarcinoma
Adult
Aged
Aged, 80 and over
Brain Neoplasms
Cohort Studies
Demography
Disease Progression
Disease-Free Survival
DNA Mutational Analysis
Female
Humans
Kaplan-Meier Estimate
Lung Neoplasms
Male
Middle Aged
Multivariate Analysis
Mutation
Neoplasm Staging
Protein Kinase Inhibitors
Receptor, Epidermal Growth Factor
Reflex
Smoking
Treatment Outcome
Issue Date: 2015
Publisher: Public Library of Science
Citation: Jain A., Lim C., Gan E.M., Ng D.Z., Ng Q.S., Ang M.K., Takano A., Chan K.S., Tan W.M., Kanesvaran R., Toh C.K., Loo C.M., Hsu A.A.L., Devanand A., Lim C.H., Koong H.N., Koh T., Fong K.W., Yap S.P., Kim S.W., Chowbay B., Oon L., Lim K.H., Lim W.T., Tan E.H., Tan D.S.W. (2015). Impact of smoking and brain metastasis on outcomes of advanced EGFR mutation lung adenocarcinoma patients treated with first line epidermal growth factor receptor tyrosine kinase inhibitors. PLoS ONE 10 (5) : e0123587. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0123587
Abstract: Objectives This purpose of this study was to examine clinical-pathologic factors - particularly smoking and brain metastases - in EGFR mutation positive (M+) lung adenocarcinoma (ADC) to determine their impact on survival in patients treated with first line EGFR TKI. Methods A retrospective review of EGFR mutation reflex testing experience for all ADC diagnosed at a tertiary Asian cancer centre from January 2009 to April 2013. Amongst this cohort, patients with advanced EGFR M+ ADC treated with first line EGFR TKI were identified to determine factors that influence progression free and overall survival. Results 444/742 (59.8%) ADC reflex tested for EGFR mutations were EGFR M+. Amongst neversmokers (n=468), EGFR M+ were found in 74.5%of females and 76.3% of males, and amongst ever smokers (n=283), in 53.3% of females and 35.6%of males. Exon 20 mutations were found more commonly amongst heavy smokers (> 50 pack years and > 20 pack years, Pearson's chi square p=0.044, and p=0.038 respectively). 211 patients treated with palliative first line TKI had a median PFS and OS of 9.2 and 19.6 months respectively. 26% of patients had brain metastasis at diagnosis. This was significantly detrimental to overall survival (HR 1.85, CI 1.09-3.16, p=0.024) on multivariate analysis. There was no evidence that smoking status had a significant impact on survival. Conclusions The high prevalence of EGFR M+ in our patient population warrants reflex testing regardless of gender and smoking status. Smoking status and dosage did not impact progression free or overall survival in patients treated with first line EGFR TKI. The presence of brain metastasis at diagnosis negatively impacts overall survival. © 2015 Jain et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/165697
ISSN: 19326203
DOI: 10.1371/journal.pone.0123587
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