title: Overall survival benefits of first-line EGFR tyrosine kinase inhibitors in EGFR-mutated non-small-cell lung cancers: a systematic review and meta-analysis.
abstract: BACKGROUND
  Accumulating data shows that exon 19 deletions and L858R, both activating epidermal growth factor receptor mutations in non-small-cell lung cancers (NSCLCs), are just two different entities in terms of prognosis and treatment response to tyrosine kinase inhibitors (TKIs).
  
  
  METHODS
  A systematic review and meta-analysis of randomized controlled trials comparing TKIs with conventional chemotherapy was performed. Eight trials of 1498 patients and five trials of 1279 patients with either exon 19 deletions or L858R were included in the meta-analysis.
  
  
  RESULTS
  TKI treatment demonstrated progression-free survival benefit in patients with exon 19 deletions (hazard ratio (HR): 0.27, 95% confidence interval (CI): 0.21-0.35) and L858R (HR: 0.45, 95% CI: 0.35-0.58). Patients with exon 19 deletions had significant overall survival (OS) benefit under TKI treatment (HR: 0.72, 95% CI: 0.60-0.88). Subgroup analyses showed that irreversible TKIs, but not reversible TKIs, had statistically significant OS benefit in these patients (irreversible TKIs, HR: 0.59, 95% CI: 0.47-0.73; reversible TKIs, HR: 0.84, 95% CI: 0.69-1.02). Patients with L858R demonstrated no OS benefit under first-line TKI use (HR: 1.15, 95% CI: 0.95-1.39).
  
  
  CONCLUSIONS
  In patients with advanced NSCLC harbouring exon 19 deletions, TKIs are associated with better OS compared with conventional chemotherapy. Future clinical trials should take exon 19 deletions and L858R as distinct disease entities and evaluate the treatment efficacy separately.
authors.affiliation: Department of Hematology and Oncology, Chang-Gung Memorial Hospital, Chia-Yi 61363, Taiwan.|Graduate Institute of Clinical Medical Sciences, Chang-Gung University, Tao-Yuan 33302, Taiwan.
authors.forename: Feng-Che
authors.initials: FC
authors.lastname: Kuan
authors.affiliation: Department of Orthopaedic Surgery, Division of Sports Medicine, Chang-Gung Memorial Hospital, Chia-Yi, Taiwan.|Centre for Evidence-Based Medicine, Chang-Gung Memorial Hospital, Chia-Yi, Taiwan.|Chang-Gung University of Science and Technology, Chia-Yi, Taiwan.
authors.forename: Liang-Tseng
authors.initials: LT
authors.lastname: Kuo
authors.affiliation: Department of Public Health, Biostatistics Consulting Center, College of Medicine, Chang-Gung University, Tao-Yuan, Taiwan.
authors.forename: Min-Chi
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Department of Thoracic Medicine, Chang-Gung Memorial Hospital, Tao-Yuan 33305, Taiwan.|Department of Respiratory Therapy, College of Medicine, Chang-Gung University, Tao-Yuan, Taiwan.
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Yang
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang-Gung University, Tao-Yuan, Taiwan.
authors.forename: Chung-Sheng
authors.initials: CS
authors.lastname: Shi
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, California 94720, USA.
authors.forename: David
authors.initials: D
authors.lastname: Teng
authors.affiliation: Department of Hematology and Oncology, Chang-Gung Memorial Hospital, Chia-Yi 61363, Taiwan.|Department of Medicine, Chang-Gung University, Tao-Yuan, Taiwan.
authors.forename: Kuan-Der
authors.initials: KD
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D017384:Sequence Deletion; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors