ORCID Profile
0000-0001-9860-8505
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Publisher: American Association for Cancer Research (AACR)
Date: 10-2007
DOI: 10.1158/1078-0432.CCR-07-0216
Abstract: Purpose: Mutation of epidermal growth factor receptor (EGFR) gene has been reported to be present in non–small cell lung cancer (NSCLC) and significantly associated with female sex and never-smoking status. In this study, we extensively investigated the impact of sex and smoking on the EGFR mutation. Experimental Design: We examined EGFR exons 18 to 21 status in 1,467 NSCLC patients by direct sequencing to study the impact of sex and smoking status on the EGFR mutational spectrum. Results: Among 1,467 patients, 197 mutations were found at exon 19, 176 at exon 21, 21 at exon 18, and 24 at exon 20. To examine the independent effect of sex and smoking, the mutational status of each exon was compared between smokers and never smokers in each sex and between males and females stratified by smoking status. In females, exon 19 (P = 0.001) and exon 21 (P & 0.001) mutations were significantly less frequent in ever smokers compared with never smokers. In males, exon 19 (P & 0.001), exon 21 (P & 0.001), and exon 18 (P = 0.003) mutations were significantly less frequent in ever smokers compared with never smokers. In analysis stratified by smoking, there was no difference in sex among never smokers. However, exon 19 mutations were significantly less frequent in males compared with females among ever smokers (P = 0.003). In addition, the interactive effect of male sex and ever smoking status significantly decreased the frequency of exon 19 mutations (P = 0.047) when female never smoker was set as a reference. Conclusion: Both sex and smoking status could influence the EGFR mutational spectrum. Our findings suggest that in idual EGFR exons may have differing susceptibilities for mutagenesis.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-06-2015
Abstract: We examined the impact of different epidermal growth factor receptor (EGFR) mutations and clinical characteristics on progression-free survival (PFS) in patients with advanced EGFR-mutated non–small-cell lung cancer treated with EGFR tyrosine kinase inhibitors (TKIs) as first-line therapy. This meta-analysis included randomized trials comparing EGFR TKIs with chemotherapy. We calculated hazard ratios (HRs) and 95% CIs for PFS for the trial population and prespecified subgroups and calculated pooled estimates of treatment efficacy using the fixed-effects inverse-variance-weighted method. All statistical tests were two sided. In seven eligible trials (1,649 patients), EGFR TKIs, compared with chemotherapy, significantly prolonged PFS overall (HR, 0.37 95% CI, 0.32 to 0.42) and in all subgroups. For tumors with exon 19 deletions, the benefit was 50% greater (HR, 0.24 95% CI, 0.20 to 0.29) than for tumors with exon 21 L858R substitution (HR, 0.48 95% CI, 0.39 to 0.58 P interaction .001). Never-smokers had a 36% greater benefit (HR, 0.32 95% CI, 0.27 to 0.37) than current or former smokers (HR, 0.50 95% CI, 0.40 to 0.63 P interaction .001). Women had a 27% greater benefit (HR, 0.33 95% CI, 0.28 to 0.38) than men (HR, 0.45 95% CI, 0.36 to 0.55 treatment-sex interaction P = .02). Performance status, age, ethnicity, and tumor histology did not significantly predict additional benefit from EGFR TKIs. Although EGFR TKIs significantly prolonged PFS overall and in all subgroups, compared with chemotherapy, greater benefits were observed in those with exon 19 deletions, never-smokers, and women. These findings should enhance drug development and economic analyses, as well as the design and interpretation of clinical trials.
No related grants have been discovered for Tetsuya Mitsudomi.