Impact of Smoking Status on EGFR-TKI Efficacy for Advanced Non–Small-Cell Lung Cancer in EGFR Mutants: A Meta-analysis

Abstract

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.

The impact of smoking status on radiologic tumor progression patterns and response to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in lung adenocarcinoma with activating EGFR mutations

“…Moreover, a previous study identified an inverse relationship between incidence of EGFR mutations and number of pack-years of cigarette smoking, with fewer mutations found in patients with longer smoking history (12). Together, these findings suggest that favorable outcomes in response to EGFR-TKI therapy in non-smoking NSCLC patients are due to their higher rate of EGFR-mutation compared with that of smoking patients (16,17).…”

“…However, in our study, EGFR mutation status had no significant effect on the clinical outcome. Also, recent metaanalyses (17,30) showed that non-smokers are likely to have a longer PFS than smokers when undergoing EGFR-TKI therapy for diagnosed EGFR-mutant NSCLC. A recent study by Mitchell et al (16) concluded that controversies in the survival outcomes of smokers versus non-smokers after EGFR-TKI therapy may be due to incomplete data on smoking history, and that its relationship with treatment response has not been comprehensively analyzed.…”

“…Few studies have focused directly on smoking history and its relationship with EGFR-TKI therapy outcome in patients with EGFR-mutant NSCLC, and the existing studies have yielded controversial results (12,14,(17)(18)(19)(20). Several studies showed no significant differences in survival outcomes after EGFR-TKI therapy in lung adenocarcinoma patients who were former/current smokers and those who had never smoked (12,(18)(19)(20).…”

Factors associated with efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer

“…EGFR-TKI might be effective in patients with EGFR mutation during the initiation of the treatment since EGFR mutation plays a dominant role. However, resistance to EGFR-TKIs may occur once the dominant carcinogenic effect of EGFR mutations is replaced by other mechanisms; 48 nevertheless, specific mechanisms remain unknown. The poor response to EGFR-TKIs in patients with a smoking history could be explained by cigarette smoking-induced EGFR posttranslational changes, activation of the nicotinic acetylcholine receptor by cigarette smoking-induced EGFR-TKIs resistance, promotion of EGFR signal, and epithelialmesenchymal transition (EMT).…”

“…A meta-analysis reported that non-smoking is associated with longer PFS than ever smoking after EGFR-TKIs treatment in advanced NSCLC patients with EGFR mutations. 48 The dosage of smoking may affect the EGFR-TKIs efficacy. The smoking dosage of ≥30 pack-years is an independent negative predictor of the efficacy of EGFR-TKIs in lung adenocarcinoma patients with activating EGFR mutations.…”