title: Analysis of progression-free survival of first-line tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring leu858Arg or exon 19 deletions.
abstract: BACKGROUND
  Gefitinib, erlotinib and afatinib provide remarkable response rates and progression-free survival compared to platinum-based chemotherapy in patients with non-small cell lung cancer harboring epidermal growth factor receptor-activating mutations, and are therefore standard first-line treatment in these patients. However, no study has compared these drugs regarding progression-free survival.
  
  
  METHODS
  We conducted this retrospective study at a single medical center in Taiwan from February 16, 2011 to October 30, 2015. We used the Kaplan-Meier method to estimate survival, and multivariate Cox proportional hazard models to estimate adjusted hazard ratios and 95% confidence intervals.
  
  
  RESULTS
  Of the 1006 patients diagnosed with stage IIIb and IV non-small cell lung cancer in the study period, 448 (44.5%) had EGFR-activating mutations and received first-line therapy with gefitinib (n = 304, 67.6%), erlotinib (n = 63, 14.3%), or afatinib (n = 81, 18.1%). The median duration of follow-up for progression-free survival was 12.1 months in the gefitinib arm (Interquartile range [IQR]: 5.5-16.5), 11.2 months in the erlotinib arm (IQR: 4.9-16.7), and 10.3 months in the afatinib arm (IQR: 7.0-14.2). Progression-free survival was significantly longer in the patients who received afatinib or erlotinib compared to those who received gefitinib (log-rank test, p < 0.001), and the median progression-free survival was 11.4 months in the gefitinib group.
  
  
  CONCLUSIONS
  Afatinib and erlotinib provide significant benefits in progression-free survival compared to gefitinib in first-line treatment of patients with non-small-cell lung cancers harboring EGFR-activating mutations. Further clinical trials are warranted to validate these findings.
authors.affiliation: Department of Hematology and Oncology, Department of Medicine, Chang-Gung Memorial Hospital, Chiayi 61363, Taiwan.|Graduate Institute of Clinical Medical Sciences, Chang-Gung University, Taoyuan 33302, Taiwan.
authors.forename: Feng-Che
authors.initials: FC
authors.lastname: Kuan
authors.affiliation: Department of Thoracic Medicine, Chang-Gung Memorial Hospital, Taoyuan 33305, Taiwan.
authors.forename: Shih-Hong
authors.initials: SH
authors.lastname: Li
authors.affiliation: Department of Thoracic Medicine, Chang-Gung Memorial Hospital, Taoyuan 33305, Taiwan.|Department of Medicine, Chang-Gung University, Taoyuan 33302, Taiwan.
authors.forename: Chih-Liang
authors.initials: CL
authors.lastname: Wang
authors.affiliation: Cencer of Excellence for Chang Gung Research Datalink, Chang-Gung Memorial Hospital, Chiayi 61363, Taiwan.
authors.forename: Meng-Hung
authors.initials: MH
authors.lastname: Lin
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Medicine, Chang-Gung Memorial Hospital, Chiayi 61363, Taiwan.|Department of Respiratory Therapy, Chang-Gung University, Taoyuan 33302, Taiwan.
authors.forename: Ying-Huang
authors.initials: YH
authors.lastname: Tsai
authors.affiliation: Department of Thoracic Medicine, Chang-Gung Memorial Hospital, Taoyuan 33305, Taiwan.|Department of Respiratory Therapy, Chang-Gung University, Taoyuan 33302, Taiwan.
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Yang
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Leu858Arg; Thr790Met; afatinib; erlotinib; gefitinib