Abstract
BackgroundAlthough lung adenocarcinoma with activating epidermal growth factor receptor (EGFR) mutations is common in never smokers, one-third of the patients are ever-smokers. We aimed to investigate the effect of cumulative smoking dose(CSD) on clinical outcomes, including progression-free survival (PFS) and overall survival (OS), in patients with EGFR-mutated lung adenocarcinoma receiving EGFR-tyrosine kinase inhibitors (TKIs).MethodsWe retrospectively analyzed 142 patients with EGFR-mutation positive advanced or recurrent lung adenocarcinoma who were administered gefitinib, erlotinib, afatinib, and osimertinib. These patients were classified based on their CSD as never smokers, light smokers (≤10 pack-years [PYs]), moderate smokers (11–30 PYs), and heavy smokers (> 30 PYs). PFS and OS were analyzed according to smoking subgroups via Kaplan-Meier curves.ResultsAmong the 142 patients, 91 (64.1%), 12 (8.5%), 22 (15.5%), and 17 (12%) were never, light, moderate, and heavy smokers, respectively. CSD was inversely associated with median PFS in a statistically significant dose-dependent manner (11.8 months (mo), 11.0 mo, 7.4 mo, and 3.9 mo; p < 0.001). Statistically significant negative association was observed between CSD and median OS (33.6 mo, 26.3 mo, 20 mo, and 8.9 mo; p < 0.001). In the multivariate analysis adjusted for age, sex, performance status, stage, and timing of EGFR-TKIs, CSD was an independent predictive factor for disease progression (hazard ratio [HR], 4.00; 95% confidence interval [CI], 1.95–8.23; p = 0.012) and OS (HR, 3.9; 95% CI, 1.84–8.28; p < 0.001).ConclusionCSD is an important predictive and prognostic factor in patients with EGFR-mutated lung adenocarcinoma, and associated smoking-related gene signatures might affect the outcomes.
Highlights
Lung adenocarcinoma with activating epidermal growth factor receptor (EGFR) mutations is common in never smokers, one-third of the patients are ever-smokers
Patient characteristics A total of 142 patients with advanced or recurrent lung adenocarcinoma with susceptible EGFR mutation treated at Konkuk University Medical Center, Seoul, Korea were retrospectively reviewed between January 2006 and November 2016
We evaluated the histopathology of the 94 patients of the total 143 patients by 2015 WHO classification of lung tumors but could not classify the pathologic type of other patients because their data were from bronchial washing (n = 10), pleural fluid (n = 19) and metastatic tissue (n = 14)
Summary
Lung adenocarcinoma with activating epidermal growth factor receptor (EGFR) mutations is common in never smokers, one-third of the patients are ever-smokers. We aimed to investigate the effect of cumulative smoking dose(CSD) on clinical outcomes, including progression-free survival (PFS) and overall survival (OS), in patients with EGFR-mutated lung adenocarcinoma receiving EGFR-tyrosine kinase inhibitors (TKIs). Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment has become a standard therapy for patients with advanced lung adenocarcinoma harboring activating EGFR mutations. The effect of CSD on PFS and overall survival (OS) in patients with EGFR-mutated lung adenocarcinoma is yet to be clarified, and only few studies have directly focused on the relationship between the efficacy of EGFR-TKI and CSD in patients with EGFR-mutated lung adenocarcinoma In this retrospective study, we reviewed the medical records, including the smoking history of patients with positive EGFR mutations who were treated with EGFR-TKIs. We investigated whether CSD was an independent factor affecting the PFS, OS, and efficacy of EGFR-TKI in patients with EGFR mutation-positive adenocarcinoma. Nucleotide sequencing was analyzed by PyroMark ID System and SNP reagent kit (both purchased from Biotage, Uppsala, Sweden). [17]
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