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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 
 LUNG CANCER, Vol.84(2) : 196-202, 2014 
Journal Title
Issue Date
Adenocarcinoma/drug therapy* ; Adenocarcinoma/etiology ; Adenocarcinoma/genetics ; Adenocarcinoma/mortality ; Antineoplastic Agents/pharmacology* ; Antineoplastic Agents/therapeutic use ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Erlotinib Hydrochloride ; Female ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/drug therapy* ; Lung Neoplasms/etiology ; Lung Neoplasms/genetics ; Lung Neoplasms/mortality ; Male ; Middle Aged ; Multivariate Analysis ; Mutation, Missense ; Prognosis ; Proportional Hazards Models ; Protein Kinase Inhibitors/pharmacology* ; Protein Kinase Inhibitors/therapeutic use ; Quinazolines/pharmacology ; Quinazolines/therapeutic use ; Receptor, Epidermal Growth Factor/antagonists & inhibitors ; Receptor, Epidermal Growth Factor/genetics* ; Retrospective Studies ; Sequence Deletion ; Smoking/adverse effects* ; Treatment Outcome
Cigarette smoking ; EGFR mutation ; EGFR-tyrosine kinase inhibitors ; Lung adenocarcinoma ; Prognosis ; Response rate
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.
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.
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).
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.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Preventive Medicine (예방의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kang, Dae Ryong(강대용)
Kim, Min Hwan(김민환) ORCID logo https://orcid.org/0000-0002-1595-6342
Kim, Eun Young(김은영) ORCID logo https://orcid.org/0000-0002-3281-5744
Kim, Joo Hang(김주항)
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Bae, Mi Kyung(배미경)
Lee, Jae Seok(이재석)
Lee, Chang Young(이창영)
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
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