title: Effectiveness of gefitinib against non-small-cell lung cancer with the uncommon EGFR mutations G719X and L861Q.
abstract: BACKGROUND
  In non-small-cell lung cancer, an exon 19 deletion and an L858R point mutation in the epidermal growth factor receptor (EGFR) are predictors of a response to EGFR-tyrosine kinase inhibitors. However, it is uncertain whether other uncommon EGFR mutations are associated with sensitivity to EGFR-tyrosine kinase inhibitors.
  
  
  METHODS
  A post-hoc analysis to assess prognostic factors was performed with the use of patients with EGFR mutations (exon 19 deletion, L858R, G719X, and L861Q) who were treated with gefitinib in the NEJ002 study, which compared gefitinib with carboplatin-paclitaxel as the first-line therapy.
  
  
  RESULTS
  In the NEJ002 study, 225 patients with EGFR mutations received gefitinib at any treatment line. The Cox proportional hazards model indicated that performance status, response to chemotherapy, response to gefitinib, and mutation types were significant prognostic factors. Overall survival (OS) was significantly shorter among patients with uncommon EGFR mutations (G719X or L861Q) compared with OS of those with common EGFR mutations (12 versus 28.4 months; p = 0.002). In the gefitinib group (n = 114), patients with uncommon EGFR mutations had a significantly shorter OS (11.9 versus 29.3 months; p < 0.001). By contrast, OS was similar between patients with uncommon mutations and those with common mutations in the carboplatin-paclitaxel group (n = 111; 22.8 versus 28 months; p = 0.358).
  
  
  CONCLUSIONS
  The post-hoc analyses clearly demonstrated shorter survival for gefitinib-treated patients with uncommon EGFR mutations compared with the survival of those with common mutations and suggest that the first-line chemotherapy may be relatively effective for non-small-cell lung cancer with uncommon EGFR mutations.
authors.affiliation: *Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan; †Department of Internal Medicine, Division of Pulmonary Medicine, Infections Disease, and Oncology, Nippon Medical School, Tokyo, Japan; ‡Department of Respiratory Medicine, Miyagi Cancer Center, Miyagi, Japan; §Department of Respiratory Medicine, Tohoku University, Sendai, Japan; ‖Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan; ¶Department of Medical Oncology, KKR Sapporo Medical Center, Sapporo, Japan; #Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan; **Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, Mibu, Japan; ††Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan; and ‡‡Department of Respiratory Medicine, Saitama International Medical Center, Saitama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Yuji
authors.initials: Y
authors.lastname: Minegishi
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yoshizawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Maemondo
authors.forename: Akira
authors.initials: A
authors.lastname: Inoue
authors.forename: Shunichi
authors.initials: S
authors.lastname: Sugawara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Isobe
authors.forename: Masao
authors.initials: M
authors.lastname: Harada
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Ishii
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
authors.forename: Koichi
authors.initials: K
authors.lastname: Hagiwara
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage; D012189:Retrospective Studies; D017384:Sequence Deletion; D015996:Survival Rate
chemical_list: D011799:Quinazolines; D016190:Carboplatin; C512478:EGFR protein, human; D066246:ErbB Receptors; D017239:Paclitaxel; D000077156:Gefitinib