title: Phase II study of erlotinib in recurrent or metastatic endometrial cancer: NCIC IND-148.
abstract: OBJECTIVE
  Epidermal growth factor receptor (EGFR) overexpression is common in endometrial cancers and may have a major role in tumor growth and progression. Erlotinib is an orally active, selective inhibitor of EGFR tyrosine kinase activity.
  
  
  METHODS
  A multinomial design two-stage phase II study was performed to evaluate single-agent activity of erlotinib in women with advanced endometrial cancer with recurrent or metastatic disease who were chemotherapy naïve and had received up to one line of prior hormonal therapy. Erlotinib was administered at daily dose of 150 mg. Archival tumor tissue was analyzed for EGFR expression by immunohistochemistry (IHC) and gene amplification by fluorescent in situ hybridization (FISH). Mutational status of EGFR was determined in responders.
  
  
  RESULTS
  Thirty-two of 34 entered patients are assessable for response. Treatment was well tolerated and severe toxicity infrequent, with the only grade 4 toxicity being an elevation of transaminases (AST). There were four confirmed partial responses (PRs; 12.5%; 95% CI, 3.5% to 29%) lasting 2 to 36 months. Fifteen patients had stable disease (SD), with median duration of 3.7 months (range, 2 to 12 months). EGFR expression was analyzed in thirty patients; 19 were positive, nine were negative, and two were not assessable. Of the 19 patients who were EGFR positive, three had PR (16%), seven SD, and eight progressive disease, and one was not assessable. No mutations were identified in responders. FISH showed no correlation of response with gene amplification.
  
  
  CONCLUSIONS
  Erlotinib is well tolerated with an overall objective response rate of 12.5%. Molecular analysis did not identify EGFR mutations in responders or correlation of response with gene amplification.
authors.affiliation: Princess Margaret Hospital, University Health Network, Bras Family Drug Development Program, University of Toronto, Toronto, Ontario, Canada. amit.oza@uhn.on.ca
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Eisenhauer
authors.forename: Laurie
authors.initials: L
authors.lastname: Elit
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Cutz
authors.forename: Akira
authors.initials: A
authors.lastname: Sakurada
authors.forename: Ming S
authors.initials: MS
authors.lastname: Tsao
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hoskins
authors.forename: Jim
authors.initials: J
authors.lastname: Biagi
authors.forename: Prafull
authors.initials: P
authors.lastname: Ghatage
authors.forename: John
authors.initials: J
authors.lastname: Mazurka
authors.forename: Diane
authors.initials: D
authors.lastname: Provencher
authors.forename: Naomi
authors.initials: N
authors.lastname: Dore
authors.forename: Janet
authors.initials: J
authors.lastname: Dancey
authors.forename: Anthony
authors.initials: A
authors.lastname: Fyles
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy* / Q000556:secondary; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000556:secondary; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011799:Quinazolines / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride