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

Abstract

ObjectivesThis 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.MethodsA 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.Results444/742 (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.ConclusionsThe 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.

Impact of heavy smoking on the benefits from first-line EGFR-TKI therapy in patients with advanced lung adenocarcinoma

“…The present study showed that smoking alone had no impact of PFS, but that the dose of cigarettes (>30 packs/year) is an independent factor associated with PFS. Therefore, it is possible that not only the smoking status is associated with EGFR-TKI response, but also the amount of cigarette smoke, as supported by Kim et al [ 26 ] In addition, Jain et al [ 43 ] showed that the mutation patterns were different between light and heavy smokers. Nevertheless, these results will have to be confirmed in future studies.…”

Prognostic value of cancer antigen -125 for lung adenocarcinoma patients with brain metastasis: A random survival forest prognostic model

“…Many prognostic factors had been related to the survival of NSCLC patients. Besides those in the modified-RPA and the lung-GPA model, the factors also included gene mutations and laboratory indicators 13 , 24 , 25 . However, all factors could not be simultaneously included in the prognostic model for overfitting.…”

“…Qiagen formalin fixed paraffin embedded (FFPE) DNA extraction kit was used to extract genomic DNA. Exons 18, 19, 20 and 21 of the extracted DNA were amplified by polymerase chain reaction (PCR) technique, and were analyzed by direct Sanger sequencing 13 . Because NSCLC patients with EGFR exon 20 insertion were not well respond to gefitinib or erlotinib as those with other mutations 14 , EGFR mutation status was analyzed under two classifications, ie EGFR (exon 19–21) and EGFR-20 (exon 18, 19 and 21).…”

Brain metastasis in non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations: a report of seven cases and literature review

“…The current mainstream view is that EGFR-mutated NSCLC has a higher incidence of BM, but the survival time may be longer than wild -type EGFR NSCLC because of the use of EGFR-TKIs. Today, thanks to TKIs, NSCLC patients with EGFR mutations with BM at diagnosis achieve a median survival of approximately 18 months 10 , 12 , 13 . Therefore, the higher BM incidence in the EGFR-mutated group might partly be explained with a prolonged survival in the EGFR group.…”