title: Coexistence of EGFR T790M mutation and common activating mutations in pretreatment non-small cell lung cancer: A systematic review and meta-analysis.
abstract: OBJECTIVE
  Previous studies have indicated that EGFR exon 19 deletions in non-small cell lung cancer (NSCLC) are associated with better outcomes to tyrosine kinase inhibitors (TKIs) than the L858R mutation. This study aimed to evaluate whether T790M, a resistant mutation, is more likely to coexist with L858R mutation than with exon 19 deletions in pretreatment NSCLC patients.
  
  
  METHODS
  We searched MEDLINE and EMBASE up to Nov 30th, 2015 to identify randomized controlled trials (RCTs) and observational studies that reported pretreatment T790M and EGFR-activating mutation. A meta-analysis was performed using a random-effects model. The primary outcome was odds ratio (OR) of pretreatment T790M mutation in NSCLC co-existing with L858R mutation and exon 19 deletions. Stratified analysis was performed based on sensitivity of mutation detection methods for T790M.
  
  
  RESULTS
  We identified 15 observational studies and 3 RCTs for analysis. Pretreatment T790M was more frequent in L858R than in exon 19 mutated patients. The association of T790M and L858R was statistically significant in observational studies (OR, 1.65, 95% CI, 1.17-2.32), with less precision in RCTs (OR, 1.84, 95% CI, 0.96-3.52). In the stratified analysis based on the sensitivity of the mutation detection methods, the association was observed in the studies using intermediately (detection limit <5% and ≥ 0.1%; OR, 2.23, 95% CI, 1.19-4.17) and highly sensitive methods (detection limit <0.1%; OR, 1.74, 95% CI, 1.10-2.73), but not in those using low sensitivity methods (detection limit >5%; OR, 1.28, 95% CI, 0.74-2.23).
  
  
  CONCLUSIONS
  Pretreatment EGFR T790M mutation is more likely to coexist with L858R mutation than with exon 19 deletions in NSCLC. This association was observed only in studies using sensitive mutation detection methods (<5%).
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, 7 Chung Shan South Road, Taipei 100, Taiwan.
authors.forename: Li-Yang
authors.initials: LY
authors.lastname: Chen
authors.affiliation: Breakthrough Cancer Research Unit, Pangaea Biotech S.L, Sabino Arana, 5-19, Barcelona 08028, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Molina-Vila
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, 7 Chung Shan South Road, Taipei 100, Taiwan.
authors.forename: Sheng-Yuan
authors.initials: SY
authors.lastname: Ruan
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, 1 Chang-Te Street, Taipei 100, Taiwan.
authors.forename: Kang-Yi
authors.initials: KY
authors.lastname: Su
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, 7 Chung Shan South Road, Taipei 100, Taiwan.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Liao
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, 7 Chung Shan South Road, Taipei 100, Taiwan.
authors.forename: Kai-Lun
authors.initials: KL
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, 7 Chung Shan South Road, Taipei 100, Taiwan. Electronic address: ccho1203@ntu.edu.tw.
authors.forename: Chao-Chi
authors.initials: CC
authors.lastname: Ho
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, 7 Chung Shan South Road, Taipei 100, Taiwan.
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Shih
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, 7 Chung Shan South Road, Taipei 100, Taiwan.
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.affiliation: Graduate Institute of Oncology and Cancer Research Centre, College of Medicine, National Taiwan University, 7 Chung Shan South Road, Taipei 100, Taiwan.
authors.forename: James Chih-Hsin
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet s/n, 08916 Badalona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.affiliation: National Taiwan University, 1 Roosevelt Road Sec. 4, Taipei 100, Taiwan.
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000628:therapy; D003062:Codon; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000628:therapy; D009154:Mutation; D016017:Odds Ratio; D011379:Prognosis
chemical_list: D003062:Codon; D066246:ErbB Receptors
keywords: Epidermal growth factor receptor; Exon 19 deletions; L858R; Meta-analysis; Non-small cell lung cancer; T790M