title: Erlotinib after gefitinib failure in relapsed non-small cell lung cancer: clinical benefit with optimal patient selection.
abstract: BACKGROUND
  Recent reports have suggested that erlotinib therapy after gefitinib failure requires optimal patient selection to obtain clinical benefits in relapsed non-small cell lung cancer (NSCLC). However, insufficient evidence exists to determine which clinical factors best identify patients who benefit from erlotinib therapy.
  
  
  METHODS
  One hundred twenty-five patients with relapsed NSCLC who had received erlotinib therapy after gefitinib failure were retrospectively evaluated between January 2008 and May 2009.
  
  
  RESULTS
  The response rate (RR), disease control rate (DCR), and median progression-free survival (PFS) for all patients were 9% (95% confidence interval [CI], 5-15%), 44% (95% CI, 35-53%), and 2.0 months (95% CI, 1.4-2.5 months), respectively. The median survival time was estimated to be 11.8 months (95% CI, 6.4-16.0 months). Using multivariate analysis, good performance status (PS), EGFR mutation-positive status, and benefit from prior gefitinib therapy were identified as significant predictive factors for disease control. Using a proportional hazards model, benefit from prior gefitinib therapy, good PS, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies emerged as significant predictive factors for longer PFS. Thirty-two patients with concomitant PS 0/1, benefit from prior gefitinib therapy, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies benefitted more from erlotinib therapy: RR, 25% (95% CI, 12-43%); DCR, 72% (95% CI, 53-86%); and median PFS, 3.4 months (95% CI, 2.4-4.9 months).
  
  
  CONCLUSIONS
  Higher efficacy of erlotinib after gefitinib failure can be achieved with proper patient selection criteria, including good PS, benefit from prior gefitinib therapy, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies.
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima-minamimachi, Chuo-ku, Kobe, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Hata
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujita
authors.forename: Kei
authors.initials: K
authors.lastname: Kunimasa
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nanjo
authors.forename: Kyoko
authors.initials: K
authors.lastname: Otsuka
authors.forename: Reiko
authors.initials: R
authors.lastname: Kaji
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tomii
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwasaku
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ishida
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D018773:Genes, erbB-1 / Q000235:genetics; D006801:Humans; D007342:Insurance Benefits / Q000706:statistics & numerical data; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009364:Neoplasm Recurrence, Local; D018579:Patient Selection; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib