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
Open accessAbstract
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 never-smokers (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.
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- 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.
- Affiliations
- National Cancer Centre Singapore (SG)
- National University of Singapore (SG)
- Singapore General Hospital (SG)
- Corresponding author
- Jain, Amit
- Lim, Cindy
- Gan, Eugene MingJin
- Ng, David Zhihao
- Ng, Quan Sing
- Ang, Mei Kim
- Takano, Angela
- Chan, Kian Sing
- Tan, Wu Meng
- Kanesvaran, Ravindran
- Toh, Chee Keong
- Loo, Chian Min
- Hsu, Anne Ann Ling
- Lim, Chong Hee
- Koong, Heng Nung
- Koh, Tina
- Fong, Kam Weng
- Yap, Swee Peng
- Kim, Su Woon
- Chowbay, Balram
- Oon, Lynette
- Lim, Kiat Hon
- Lim, Wan Teck
- Tan, Eng Huat
- Tan, Daniel Shao Weng
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-05-08
- Volume
- 10
- Issue
- 5
- Pages
- e0123587
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4425557
- OpenAlex
- W1579407204
- Cited by
- 32
- References
- 26
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 10 · 2017: 5 · 2016: 3 · 2015: 1
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Cancer Centre of Singapore
- Singapore Millennium Foundation
- Medical Research Council
- National Medical Research Council
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- EGFR mutation, lung adenocarcinoma, smoking, brain metastases, EGFR tyrosine kinase inhibitors, first-line therapy, progression-free survival, overall survival, exon 20 mutations, reflex testing, prognostic factors
- MeSH terms
- Adenocarcinoma of Lung, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Brain Neoplasms, Demography, DNA Mutational Analysis, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Neoplasm Staging, Reflex, Smoking, Cohort Studies, Multivariate Analysis, Treatment Outcome, Disease Progression, Disease-Free Survival, Protein Kinase Inhibitors, Kaplan-Meier Estimate, ErbB Receptors
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