title: First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study.
abstract: BACKGROUND
  Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  
  
  
  METHODS
  gefitinib 250 mg day(-1) until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples.
  
  
  RESULTS
  Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8%; adenocarcinoma 97.2%; never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5-77.7), DCR 90.6% (95% CI 83.5-94.8), median PFS 9.7 months (95% CI 8.5-11.0), median OS 19.2 months (95% CI 17.0-NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15%; SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8-74.7).
  
  
  CONCLUSIONS
  First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable.
authors.affiliation: Institut de Cancérologie de l'Ouest, Centre René Gauducheau, Bd J. Monod, 44805 St-Herblain, Nantes, France.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Douillard
authors.affiliation: National Koranyi Institute of Pulmonology, Piheno ut 1, Budapest H-1121, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Ostoros
authors.affiliation: Hospital Regional Universitario Carlos Haya, Málaga, Andalucia 29010, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Cobo
authors.affiliation: Institutul Oncologic Ion Chiricuta and UMF Iuliu Hatieganu, Cluj-Napoca 400015, Romania.
authors.forename: T
authors.initials: T
authors.lastname: Ciuleanu
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: R
authors.initials: R
authors.lastname: McCormack
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: A
authors.initials: A
authors.lastname: Webster
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: T
authors.initials: T
authors.lastname: Milenkova
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000097:blood / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib