title: Effect of smoking status on progression-free and overall survival in non-small cell lung cancer patients receiving erlotinib or gefitinib: a meta-analysis.
abstract: OBJECTIVE
  Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib or gefitinib are indicated for the treatment of non-small cell lung cancer (NSCLC). EGFR tyrosine kinase domain mutations have been reported to be associated with EGFR-TKI response in patients with NSCLC. Certain patient subgroups in which EGFR somatic mutations are more frequently observed are thought to derive more clinical benefit from EGFR-TKI therapy. We performed a systematic review and meta-analysis to summarize the evidence regarding the association of smoking status with overall survival (OS) and progression-free survival (PFS) in patients with NSCLC receiving EGFR-TKI therapy with erlotinib or gefitinib.
  
  
  METHODS
  Eligible studies were selected by two independent reviewers using the inclusion and exclusion criteria predefined in the protocol. Eligible studies included those evaluating the association of smoking status with OS and PFS in patients with NSCLC receiving erlotinib or gefitinib. Non-clinical studies, case reports, non-peer-reviewed abstracts and non-relevant studies were excluded.
  
  
  CONCLUSIONS
  Data on OS and PFS in patients with NSCLC treated with EGFR-TKIs were available in nine and ten trials, respectively. The OS and PFS from both the treatment and control groups were not significantly different between never smokers and former or current smokers (OS: odds ratio [OR], 0·80; 95% confidence interval [CI], 0·63-1·09; PFS: OR, 0·75; 95% CI, 0·49-1·14), respectively. However, in comparison within each smoking group, EGFR-TKI treatment led to more favourable OS and PFS in never smokers (OS: OR, 0·55; 95% CI, 0·42-0·73; PFS: OR, 0·43; 95% CI, 0·33-0·54), compared with former or current smokers (OS: OR, 0·89; 95% CI, 0·80-0·97; PFS: OR, 0·73; 95% CI, 0·62-0·85).
  
  
  CONCLUSIONS
  Among patients with NSCLC receiving EGFR-TKI therapy with erlotinib or gefitinib, never smokers appear to show longer OS and PFS as compared to former or current smokers. However, this is based on indirect comparisons and more robust larger head-to-head trials are required for more robust inferences.
authors.affiliation: Graduate School of Clinical Pharmacy, CHA University, Gyeonggi-do, Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Sohn
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea.
authors.forename: J-W
authors.initials: JW
authors.lastname: Kwon
authors.affiliation: College of Pharmacy, Ajou University, Suwon, Korea.
authors.forename: S
authors.initials: S
authors.lastname: Shin
authors.affiliation: College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: H-S
authors.initials: HS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*; D012907:Smoking / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: erlotinib; gefitinib; non-small cell lung cancer; smoking