Impact of cigarette smoking on response to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in lung adenocarcinoma with activating EGFR mutations

Min Hwan Kim, Hye Ryun Kim, Byoung Chul Cho, Mi Kyung Bae, Eun Young Kim, Chang Young Lee, Jae Seok Lee, Dae Ryong Kang, Joo Hang Kim

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41 Citations (Scopus)


Objectives: The aim of this study is to evaluate the predictive impact of cigarette smoking on treatment outcomes of EGFR-tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma patients with activating EGFR mutations. Methods: We retrospectively analyzed 222 consecutive recurrent or unresectable lung adenocarcinoma patients who harbored activating EGFR mutations (exon 19 deletion or exon 21 L858R) and had received gefitinib or erlotinib. Detailed smoking histories were obtained from all patients according to a standard protocol. Results: Of 222 EGFR-mutated patients, 65.3% were never-smokers, 19.8% were smokers with <30 pack-years, and 14.9% were smokers with ≥30 pack-years smoking dosage. The disease control rate (DCR) and objective response rate (ORR) of smokers with ≥30 pack-years were significantly lower than never-smokers and smokers with <30 pack-years (DCR, 78.8% vs. 93.1%, p= 0.016; ORR, 45.5% vs. 62.4%, p= 0.020). Smokers with ≥30 pack-years showed significantly shorter PFS than never-smokers (6.4 vs. 11.8 months, p= 0.001) and smokers with <30 pack-years (6.4 vs. 11.4 months, p= 0.033), as well as shorter overall survival from the time of metastatic diagnosis than never-smokers (33.6 vs. 46.2 months, p= 0.003). There was no survival difference between smokers with <30 pack-year and never smokers. In the multivariate analysis adjusted for age, sex, performance status, initial stage, and line of EGFR-TKI, the presence of smoking dosage ≥30 pack-years was an independent predictive factor for the disease progression to EGFR-TKIs (hazard ratio, 1.87; 95% confidence interval, 1.15-3.05; p= 0.012). Conclusions: Cigarette smoking dosage of ≥30 pack-years is an independent negative predictive factor of EGFR-TKI treatment outcome in lung adenocarcinoma patients with activating EGFR mutations.

Original languageEnglish
Pages (from-to)196-202
Number of pages7
JournalLung Cancer
Issue number2
Publication statusPublished - 2014 May


All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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