Impact of smoking status on EGFR-TKI efficacy for advanced non-small-cell lung cancer in EGFR mutants: a meta-analysis

Background: The strong association between smoking history and the presence of epidermal growth factor receptor (EGFR) mutations has been proven in non-small-cell lung cancer (NSCLC), which explains the favorable response to EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy in nonsmoking NSCLC patients. However, few studies directly focus on the relationship between EGFR-TKI's efficacy and smoking history in NSCLC EGFR-mutant patients.

Methods: Electronic databases were searched for eligible literatures. Data on objective response rates, disease control rates, and progression-free survival (PFS) stratified by smoking status were extracted and synthesized on the basis of a random-effect model. Subgroup and sensitivity analyses were conducted.

Results: A total of 9 studies that involved a total of 1029 EGFR-mutant advanced NSCLC patients after EGFR-TKI treatment were included. In overall, nonsmoking was associated with significant prolonged PFS (HR, 0.73, 0.60 to 0.88; P = .001) compared to ever smokers. However, only marginal improvements without statistical significance in objective response rates (odds ratio, 1.11; 95% confidence interval, 0.85 to 1.46; P = .433) and disease control rate (odds ratio, 1.04; 95% confidence interval, 0.82 to 1.33; P = .740) were observed. Subgroup analyses showed that the benefits of PFS in nonsmokers were predominantly presented in pooled results of studies enrolling patients with active EGFR mutations, studies involving previously treated patients, and retrospective studies. Additionally, we failed to observe any significant benefit from nonsmokers in every subgroup for objective response rates and disease control rate.

Conclusion: For advanced NSCLC patients with EGFR mutations, nonsmoking is associated with longer PFS than ever smoking after EGFR-TKIs treatment. Smoking history should be considered an essential factor in studies regarding EGFR-targeted agents toward EGFR-mutant patients.