title: Impact of smoking status on EGFR-TKI efficacy for advanced non-small-cell lung cancer in EGFR mutants: a meta-analysis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shiyang
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Fang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Shaodong
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Qin
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sheng
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address: zhangli6@mail.sysu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: EGFR mutation; Meta-analysis; Non–small-cell lung cancer; Smoking; TKI