title: Final survival and safety results from a multicenter, open-label, phase 3b trial of erlotinib in patients with advanced nonsmall cell lung cancer.
abstract: BACKGROUND
  Erlotinib is an orally available, reversible inhibitor of epidermal growth factor receptor (EGFR) with a proven survival advantage for patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) who have failed a prior chemotherapy. This phase 3b, multicenter, open-label trial of erlotinib in patients with advanced NSCLC who had progressed after standard chemotherapy treatment was conducted to examine the efficacy and safety of erlotinib monotherapy in patients with advanced NSCLC who had developed disease progression after previous chemotherapy and to characterize the duration of survival and the response rate of erlotinib-treated patients in subpopulations defined by other patient characteristics before U.S. Food and Drug Administration approval.
  
  
  METHODS
  A total of 229 patients were enrolled and treated with the standard dose of erlotinib (150 mg once daily). The coprimary objectives were to characterize the overall response rate (ORR) and overall survival (OS) associated with erlotinib therapy in this group and in patient subsets defined by tobacco history. Secondary objectives were to assess safety, to characterize OS and ORR in patient subpopulations, and to determine duration of time on treatment. Patients could remain on study up to 9 months after approval.
  
  
  RESULTS
  The ORR was 8.3% (95% confidence interval [95% CI], 5.2-2.4%). The ORR in never-smokers, previous smokers, and current smokers was 28.6% (95% CI, 13.2-50.6%), 6.0% (95% CI, 3.0-10.4%), and 7.3% (95% CI, 2.0-19.0%), respectively. The median OS for all patients was 6.3 months (95% CI, 4.7-8.0 months). In previous and current smokers, the median survival was 5.2 months (95% CI, 4.2-7.3 months) and 6.3 months (95% CI, 3.6-9.2 months), respectively, and was not reached in never-smokers. The median duration of treatment was 10.6 weeks. One (0.4%) interstitial lung disease-like event was reported.
  
  
  CONCLUSIONS
  No new safety signals were noted. The observed ORR and survival data are consistent with results from the pivotal trial BR.21.
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee 37203, USA. dspigel@tnonc.com
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: Ming
authors.initials: M
authors.lastname: Lin
authors.forename: Vincent
authors.initials: V
authors.lastname: O'Neill
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000208:ethnology / Q000401:mortality; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005006:Ethnicity; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000208:ethnology / Q000401:mortality; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D012737:Sex Factors; D012907:Smoking; D016019:Survival Analysis
chemical_list: D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors