title: Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial.
abstract: BACKGROUND
  Patients with non-small-cell lung cancer harbouring mutations in the epidermal growth factor receptor (EGFR) gene respond well to the EGFR-specific tyrosine kinase inhibitor gefitinib. However, whether gefitinib is better than standard platinum doublet chemotherapy in patients selected by EGFR mutation is uncertain.
  
  
  METHODS
  We did an open label, phase 3 study (WJTOG3405) with recruitment between March 31, 2006, and June 22, 2009, at 36 centres in Japan. 177 chemotherapy-naive patients aged 75 years or younger and diagnosed with stage IIIB/IV non-small-cell lung cancer or postoperative recurrence harbouring EGFR mutations (either the exon 19 deletion or L858R point mutation) were randomly assigned, using a minimisation technique, to receive either gefitinib (250 mg/day orally; n=88) or cisplatin (80 mg/m(2), intravenously) plus docetaxel (60 mg/m(2), intravenously; n=89), administered every 21 days for three to six cycles. The primary endpoint was progression-free survival. Survival analysis was done with the modified intention-to-treat population. This study is registered with UMIN (University Hospital Medical Information Network in Japan), number 000000539.
  
  
  RESULTS
  Five patients were excluded (two patients were found to have thyroid and colon cancer after randomisation, one patient had an exon 18 mutation, one patient had insufficient consent, and one patient showed acute allergic reaction to docetaxel). Thus, 172 patients (86 in each group) were included in the survival analyses. The gefitinib group had significantly longer progression-free survival compared with the cisplatin plus docetaxel goup, with a median progression-free survival time of 9.2 months (95% CI 8.0-13.9) versus 6.3 months (5.8-7.8; HR 0.489, 95% CI 0.336-0.710, log-rank p<0.0001). Myelosuppression, alopecia, and fatigue were more frequent in the cisplatin plus docetaxel group, but skin toxicity, liver dysfunction, and diarrhoea were more frequent in the gefitinib group. Two patients in the gefitinib group developed interstitial lung disease (incidence 2.3%), one of whom died.
  
  
  CONCLUSIONS
  Patients with lung cancer who are selected by EGFR mutations have longer progression-free survival if they are treated with gefitinib than if they are treated with cisplatin plus docetaxel.
  
  
  BACKGROUND
  West Japan Oncology Group (WJOG): a non-profit organisation supported by unrestricted donations from several pharmaceutical companies.
authors.affiliation: Department of Thoracic Surgery, Aichi Cancer Center Hospital, Chikusa-ku, Nagoya, Japan. mitsudom@aichi-cc.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Shunichi
authors.initials: S
authors.lastname: Negoro
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Junji
authors.initials: J
authors.lastname: Tsurutani
authors.forename: Takashi
authors.initials: T
authors.lastname: Seto
authors.forename: Miyako
authors.initials: M
authors.lastname: Satouchi
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tada
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hirashima
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Asami
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
authors.forename: Minoru
authors.initials: M
authors.lastname: Takada
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Shibata
authors.forename: Shinzoh
authors.initials: S
authors.lastname: Kudoh
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage*; D000077143:Docetaxel; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000008:administration & dosage*; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; D066246:ErbB Receptors; D002945:Cisplatin; D000077156:Gefitinib