title: Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.
abstract: OBJECTIVE
  To describe the Food and Drug Administration (FDA) review and approval of erlotinib (Tarceva, OSI Pharmaceuticals, Melville, NY) for treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen.
  
  
  METHODS
  The FDA reviewed raw data in electronic format from a randomized controlled clinical trial comparing erlotinib with placebo in patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen.
  
  
  RESULTS
  Patients were randomized in a 2:1 ratio (erlotinib, n = 488 and placebo, n = 243). Erlotinib was superior to placebo for survival, progression-free survival, and tumor response rate. Exploratory analyses indicate that epidermal growth factor receptor status may be an important predictor of the erlotinib survival effect. Rash (75% versus 17%) and diarrhea (54% versus 18%) in the erlotnib and placebo group respectively were the most common adverse events. Severe rash occurred in 9% and severe diarrhea in 6% of erlotinib-treated patients and each resulted in study discontinuation in 1% of patients. Dose reductions were required for 10% of patients with rash and 4% of patients with diarrhea.
  
  
  CONCLUSIONS
  On November 18, 2004, the FDA granted erlotinib regular approval for treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. The applicant has committed to conduct post-marketing clinical trials to assess further the effect of epidermal growth factor receptor expression, measured with immunohistochemical staining, on erlotinib treatment effect.
authors.affiliation: Division of Oncology Drug Products (HFD-150), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Rockville, MD 20857, USA. Johnsonj@cder.fda.gov
authors.forename: John R
authors.initials: JR
authors.lastname: Johnson
authors.forename: Martin
authors.initials: M
authors.lastname: Cohen
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.forename: Yeh-Fong
authors.initials: YF
authors.lastname: Chen
authors.forename: Gene M
authors.initials: GM
authors.lastname: Williams
authors.forename: John
authors.initials: J
authors.lastname: Duan
authors.forename: Jogarao
authors.initials: J
authors.lastname: Gobburu
authors.forename: Brian
authors.initials: B
authors.lastname: Booth
authors.forename: Kimberly
authors.initials: K
authors.lastname: Benson
authors.forename: John
authors.initials: J
authors.lastname: Leighton
authors.forename: Li Shan
authors.initials: LS
authors.lastname: Hsieh
authors.forename: Nallalerumal
authors.initials: N
authors.lastname: Chidambaram
authors.forename: Paul
authors.initials: P
authors.lastname: Zimmerman
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000293:Adolescent; D000328:Adult; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D017277:Drug Approval; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011788:Quality of Life; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D017211:Treatment Failure; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors