title: A retrospective analysis of 335 Japanese lung cancer patients who responded to initial gefitinib treatment.
abstract: BACKGROUND
  Gefitinib treatment results in considerably better progression-free survival compared with that of platinum doublets in the first line treatment of nonsmall-cell lung cancer (NSCLC) carrying an activating epidermal growth factor receptor (EGFR) mutation. Some patients who respond to gefitinib have an overall survival (OS) of more than 5 years, whereas other initial responders do less well. Although there has been considerable effort made to elucidate the mechanisms of acquired resistance, there have only been a few studies that addressed the effect of clinical backgrounds and treatment histories on the survival of the patients who had responded to an EGFR-tyrosine kinase inhibitor (TKI). In this study, we especially focused on the clinical benefit of EGFR-TKI administration after progression.
  
  
  METHODS
  We retrospectively analyzed consecutive patients with advanced NSCLC who were diagnosed before October 2010, treated with gefitinib after July 2002, and responded to it. The primary objective of this study was to evaluate how clinical backgrounds and treatment histories influence survival of the patients who respond to gefitinib. The secondary objectives were to evaluate the safety of long-term gefitinib use and to establish the optimal treatment sequence using a dynamic treatment regimen analysis (DTRA).
  
  
  RESULTS
  A total of 335 patients were recruited. Twenty-eight (8.4%) patients survived more than 5 years. Sixty-five and 93 patients received gefitinib as rechallenge and beyond progressive disease (BPD), respectively. A statistically significant difference in OS was observed between the patients who underwent gefitinib rechallenge and those who did not rechallenge (median: 1272 days vs. 774 days; p < 0.001), a result supported by a DTRA. Patients treated with gefitinib BPD also showed a tendency of longer survival.
  
  
  CONCLUSIONS
  Gefitinib rechallenge and BPD played a central role in long term survival of the patients who initially responded to gefitinib.
authors.affiliation: Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. Electronic address: nishinishipptruth@yahoo.co.jp.
authors.forename: K
authors.initials: K
authors.lastname: Nishino
authors.forename: F
authors.initials: F
authors.lastname: Imamura
authors.forename: S
authors.initials: S
authors.lastname: Morita
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: K
authors.initials: K
authors.lastname: Komuta
authors.forename: T
authors.initials: T
authors.lastname: Kijima
authors.forename: Y
authors.initials: Y
authors.lastname: Namba
authors.forename: T
authors.initials: T
authors.lastname: Kumagai
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: I
authors.initials: I
authors.lastname: Tachibana
authors.forename: Y
authors.initials: Y
authors.lastname: Nakazawa
authors.forename: J
authors.initials: J
authors.lastname: Uchida
authors.forename: S
authors.initials: S
authors.lastname: Minami
authors.forename: R
authors.initials: R
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Yano
authors.forename: T
authors.initials: T
authors.lastname: Okuyama
authors.forename: A
authors.initials: A
authors.lastname: Kumanogoh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077156:Gefitinib
keywords: Beyond progressive disease; EGFR-tyrosine kinase inhibitor; Long survival; Nonsmall-cell lung cancer; Rechallenge; Responders to gefitinib