title: Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR.
abstract: BACKGROUND
  Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor (EGFR) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib, but little is known about how its efficacy and safety profile compares with that of standard chemotherapy.
  
  
  METHODS
  We randomly assigned 230 patients with metastatic, non-small-cell lung cancer and EGFR mutations who had not previously received chemotherapy to receive gefitinib or carboplatin-paclitaxel. The primary end point was progression-free survival; secondary end points included overall survival, response rate, and toxic effects.
  
  
  RESULTS
  In the planned interim analysis of data for the first 200 patients, progression-free survival was significantly longer in the gefitinib group than in the standard-chemotherapy group (hazard ratio for death or disease progression with gefitinib, 0.36; P<0.001), resulting in early termination of the study. The gefitinib group had a significantly longer median progression-free survival (10.8 months, vs. 5.4 months in the chemotherapy group; hazard ratio, 0.30; 95% confidence interval, 0.22 to 0.41; P<0.001), as well as a higher response rate (73.7% vs. 30.7%, P<0.001). The median overall survival was 30.5 months in the gefitinib group and 23.6 months in the chemotherapy group (P=0.31). The most common adverse events in the gefitinib group were rash (71.1%) and elevated aminotransferase levels (55.3%), and in the chemotherapy group, neutropenia (77.0%), anemia (64.6%), appetite loss (56.6%), and sensory neuropathy (54.9%). One patient receiving gefitinib died from interstitial lung disease.
  
  
  CONCLUSIONS
  First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival, with acceptable toxicity, as compared with standard chemotherapy. (UMIN-CTR number, C000000376.)
authors.affiliation: Miyagi Cancer Center, Miyagi, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Maemondo
authors.forename: Akira
authors.initials: A
authors.lastname: Inoue
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Shunichi
authors.initials: S
authors.lastname: Sugawara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Oizumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Isobe
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
authors.forename: Masao
authors.initials: M
authors.lastname: Harada
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yoshizawa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kinoshita
authors.forename: Yuka
authors.initials: Y
authors.lastname: Fujita
authors.forename: Shoji
authors.initials: S
authors.lastname: Okinaga
authors.forename: Haruto
authors.initials: H
authors.lastname: Hirano
authors.forename: Kozo
authors.initials: K
authors.lastname: Yoshimori
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Harada
authors.forename: Takashi
authors.initials: T
authors.lastname: Ogura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ando
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Miyazawa
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Saijo
authors.forename: Koichi
authors.initials: K
authors.lastname: Hagiwara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017239:Paclitaxel / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D016190:Carboplatin; D066246:ErbB Receptors; D017239:Paclitaxel; D000077156:Gefitinib