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. 2015 May 8;10(5):e0123587.
doi: 10.1371/journal.pone.0123587. eCollection 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

Amit Jain  1 , Cindy Lim  2 , Eugene MingJin Gan  3 , David Zhihao Ng  3 , Quan Sing Ng  1 , Mei Kim Ang  1 , Angela Takano  4 , Kian Sing Chan  4 , Wu Meng Tan  1 , Ravindran Kanesvaran  1 , Chee Keong Toh  1 , Chian Min Loo  5 , Anne Ann Ling Hsu  5 , Anantham Devanand  5 , Chong Hee Lim  6 , Heng Nung Koong  7 , Tina Koh  7 , Kam Weng Fong  8 , Swee Peng Yap  8 , Su Woon Kim  8 , Balram Chowbay  9 , Lynette Oon  4 , Kiat Hon Lim  4 , Wan Teck Lim  1 , Eng Huat Tan  1 , Daniel Shao Weng Tan  10
Affiliations

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

Amit Jain et al. PLoS One. .

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 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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Conflict of interest statement

Competing Interests: The authors received funding from a registered charity source ‘Trailblazer Foundation Ltd.’ This does not alter adherence to PLOS ONE policies on sharing of data and materials.

Figures

Fig 1
Fig 1. Clinical characteristics and EGFR mutation status rates categorised by smoking status and sex.
11 patients with unknown smoking status, and 6 who had samples indeterminate for EGFR mutational status were excluded. 464/762 (60.9%) tested positive for EGFR mutations (EGFR M+). The number of patients needed to test in order to pick up 1 EGFR mutant lung adenocarcinoma in any sub-population stratified by sex and smoking status, was less than 3 patients (male ES; 1/0.357 = 2.8).
Fig 2
Fig 2. EGFR mutation rates amongst ever smokers classified by pack years.
Fig 3
Fig 3. Sites of EGFR mutations amongst 461 patients.
Fig 4
Fig 4. Kaplan-Meier plots of cohort of 211 patients treated with 1st line EGFR TKI; (a) PFS by brain metastasis in ECOG 0–1 patients, (b) PFS by brain metastasis in ECOG 2–4 patients, (c) OS by brain metastasis in ECOG 0–1 patients, and (d) OS by brain metastasis in ECOG 2–4 patients.
See this image and copyright information in PMC

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