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EGFR mutation, smoking, and gender in advanced lung adenocarcinoma.

ABSTRACT: In the current targeted therapy era, information on the effect of smoking in epidermal growth factor receptor (EGFR)-mutant lung cancer patients is scarce.In total, 11,678 adenocarcinoma patients were enrolled. Of these, 33.3% and 91.8% of male and female patients were non-smokers, respectively. An increased amount of smoking (P < 0.001 for trend), fewer smoke-free years (P < 0.001 for trend), and younger age of smoking initiation (P = 0.034 for trend) were all associated with significantly lower EGFR mutation rates. Smokers had a shorter median overall survival (OS) among both EGFR-mutant and EGFR-wild type patients (17.8 vs. 21.1 months, and 7.9 vs. 11.4 months respectively; both P < 0.001). Among patients with EGFR-mutant adenocarcinoma, younger smokers were associated with shorter OS (P = 0.047). In multivariate analysis, female gender was an independent prognostic factor for OS (hazard ratio: 0.86 [95% confidence interval {CI}: 0.80-0.93]; P < 0.001 in the EGFR-mutant group and 0.88 [95% CI: 0.81-0.96]; P = 0.004 in the EGFR-wild type group).We reviewed the National Lung Cancer database (Taiwan) to assess the impact of smoking on the EGFR mutation rate and survival in advanced lung adenocarcinoma patients during 2011 and 2014 retrospectively.Smoking was associated with lower incidence of EGFR mutation rate and reduced OS of advanced lung adenocarcinoma patients in a dose-dependent manner. In addition to EGFR mutation and smoking, gender also plays an important role in survival among these patients.

SUBMITTER: Tseng CH

PROVIDER: S-EPMC5716737 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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EGFR mutation, smoking, and gender in advanced lung adenocarcinoma.

Tseng Chien-Hua CH Chiang Chun-Ju CJ Tseng Jeng-Sen JS Yang Tsung-Ying TY Hsu Kuo-Hsuan KH Chen Kun-Chieh KC Wang Chih-Liang CL Chen Chih-Yi CY Yen Sang-Hue SH Tsai Chun-Ming CM Huang Ming-Shyan MS Ho Chao-Chi CC Yu Chong-Jen CJ Tsai Ying-Huang YH Chen Jin-Shing JS Chou Teh-Ying TY Tsai Ming-Hsun MH Chen Hsuan-Yu HY Su Kang-Yi KY Chen Jeremy J W JJW Chen Huei-Wen HW Yu Sung-Liang SL Liu Tsang-Wu TW Chang Gee-Chen GC

Oncotarget 20171012 58

<h4>Purpose</h4>In the current targeted therapy era, information on the effect of smoking in epidermal growth factor receptor (<i>EGFR</i>)-mutant lung cancer patients is scarce.<h4>Results</h4>In total, 11,678 adenocarcinoma patients were enrolled. Of these, 33.3% and 91.8% of male and female patients were non-smokers, respectively. An increased amount of smoking (<i>P</i> < 0.001 for trend), fewer smoke-free years (<i>P</i> < 0.001 for trend), and younger age of smoking initiation (<i>P</i> = ...[more]

PMID: 29228697

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Project description:Background: There is limited data on the relative survival rate of first-line therapy of gefitinib, erlotinib (first-generation epidermal growth factor receptor-tyrosine kinase inhibitor [EGFR-TKI]), and afatinib (second-generation EGFR-TKI) in patients with EGFR-mutated advanced lung adenocarcinoma in real-world data, especially in the Asian population. This study aimed to compare the relative survival rate of gefitinib, erlotinib, and afatinib in patients with EGFR-mutated advanced lung adenocarcinoma by real-world data in Taiwan. Methods: This retrospective cohort population-based study included untreated adult patients diagnosed with advanced lung adenocarcinoma who were identified in the Taiwan National Health Insurance Research Database between 2014 and 2017. The date of EGFR-mutated advanced lung adenocarcinoma diagnosis was referred as index date. This outcome evaluated overall survival (OS) and time to treatment failure (TTF) between gefitinib, erlotinib, and afatinib. Switching EGFR-TKIs or chemotherapy and new development of brain metastases were proxies of TTF. Estimated relative treatment effects on OS and TTF among EGFR-TKIs were adjusted by inverse probability of treatment weighting (IPTW) in Cox proportional hazards model. Propensity score (PS) matched pair analyses were performed as sensitivity analyses. Results: The study cohort included 3,695 patients initiated with gefitinib, 3,310 with erlotinib, and 3,041 with afatinib. The mean age among the three treatment groups was 70.4 (±11.6), 66.8 (±11.6), and 64.3 (±11.4) years, and the female percentage was 70.4, 58.6, and 57.7%, respectively. Afatinib showed longer median OS than gefitinib (23.9 vs. 21.3 months; adjusted hazard ratio (aHR), 0.87; p < 0.001) and erlotinib (23.9 vs. 21.8 months; aHR, 0.87; p = 0.001). Consistent results were observed with TTF outcomes. For patients with brain metastases at diagnosis, afatinib showed similar OS with erlotinib (p = 0.917) but superior to gefitinib (p = 0.028). PS matching had similar results with IPTW adjustment in the study population. Conclusion: Afatinib as first-line therapy had better survival outcomes for EGFR-mutated advanced lung adenocarcinoma than gefitinib and erlotinib in the Taiwan population. Both erlotinib and afatinib demonstrated superior treatment effect in patients with initial brain metastases than gefitinib.

Dataset Information

EGFR mutation, smoking, and gender in advanced lung adenocarcinoma.

Publications

EGFR mutation, smoking, and gender in advanced lung adenocarcinoma.

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