title: Combined survival analysis of prospective clinical trials of gefitinib for non-small cell lung cancer with EGFR mutations.
abstract: OBJECTIVE
  Somatic mutations of the epidermal growth factor receptor (EGFR) gene are associated with an increased response to gefitinib in patients with non-small cell lung cancer. We have examined the impact of gefitinib on progression-free survival and overall survival in patients with EGFR mutation-positive non-small cell lung cancer.
  
  
  METHODS
  We searched for all clinical trials that prospectively evaluated the efficacy of gefitinib for advanced non-small cell lung cancer with EGFR mutations in Japan. We did a combined analysis based on individual patient data from the identified trials.
  
  
  RESULTS
  Seven eligible trials were identified for a total of 148 non-small cell lung cancer patients with EGFR mutations. The overall response rate to gefitinib was 76.4% [95% confidence interval (95% CI), 69.5-83.2]. The median progression-free survival and overall survival were 9.7 months (95% CI, 8.2-11.1) and 24.3 months (95% CI, 19.8-28.2), respectively. Good performance status and chemotherapy-naïve status were significantly associated with a longer progression-free survival or overall survival. Of the 148 patients, 87 received gefitinib as a first-line therapy, whereas 61 received systemic chemotherapy before gefitinib treatment. The median progression-free survival after the start of first-line therapy was significantly longer in the gefitinib-first group than in the chemotherapy-first group (10.7 versus 6.0 months; P < 0.001), whereas no significant difference in median overall survival was apparent between the two groups (27.7 versus 25.7 months; P = 0.782).
  
  
  CONCLUSIONS
  Gefitinib monotherapy confers substantial clinical benefit in terms of progression-free survival and overall survival in non-small cell lung cancer patients with EGFR mutations. Randomized trials comparing chemotherapy with gefitinib as a first-line treatment are warranted in such patients.
authors.affiliation: Department of Biostatistics and Epidemiology, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Hajime
authors.initials: H
authors.lastname: Asahina
authors.forename: Akira
authors.initials: A
authors.lastname: Inoue
authors.forename: Koichi
authors.initials: K
authors.lastname: Hagiwara
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sunaga
authors.forename: Noriko
authors.initials: N
authors.lastname: Yanagitani
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.forename: Kimihide
authors.initials: K
authors.lastname: Yoshida
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hirashima
authors.forename: Kosei
authors.initials: K
authors.lastname: Yasumoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugio
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D011799:Quinazolines / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib