title: Erlotinib therapy after initial platinum doublet therapy in patients with EGFR wild type non-small cell lung cancer: results of a combined patient-level analysis of the NCIC CTG BR.21 and SATURN trials.
abstract: BACKGROUND
  The clinical benefit of erlotinib in treating epidermal growth factor receptor (EGFR) wildtype non-small cell lung cancer (NSCLC) has been questioned. We examined the impact of erlotinib in confirmed EGFR wildtype patients in two placebo-controlled phase III trials: the National Cancer Institute of Canada Clinical Trials Group BR.21 (BR.21) and Sequential Tarceva in Unresectable Non-Small Cell Lung Cancer (SATURN) trials.
  
  
  METHODS
  Combined re-analysis of progression-free survival (PFS) and overall survival (OS) in patients with known wildtype EGFR, estimated by Kaplan-Meier curves and compared by two-sided log-rank test. Cox proportional hazards model was used to estimate hazard ratios (HR) adjusted for potential confounders. Additional analyses assessed comparability of patients with known and unknown EGFR mutation status to determine generalizability of the two study populations.
  
  
  RESULTS
  Mutation status was known in 25% (n=184 of 731) of the BR.21, and 49% (n=437 of 889) of the SATURN populations, of which 82% (n=150) and 89% (n=388) respectively had wildtype EGFR. HR for PFS was 0.71 (95% CI, 0.59-0.85; P<0.01) and for OS was 0.72 (95% CI, 0.59-0.88; P<0.01). Baseline characteristics and outcome (PFS and OS) distributions were similar for patients with known and unknown EGFR status, suggesting generalizability of the EGFR wildtype data. Erlotinib benefit was sustained in all clinical subsets.
  
  
  CONCLUSIONS
  Erlotinib provided a consistent and significant improvement in survival for patients with EGFR wildtype NSCLC in both studies, individually and in combination. The benefit of erlotinib does not appear to be limited to patients with activating mutations of EGFR.
authors.affiliation: 1 Multidisciplinary Thoracic Oncology Program, Baptist Cancer Center, Memphis, TN, USA ; 2 Department of Oncology, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy ; 3 Institute of Oncology Ion Chiricuta, Cluj-Napoca, Romania ; 4 Genentech Inc., South San Francisco, CA, USA ; 5 F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Raymond U
authors.initials: RU
authors.lastname: Osarogiagbon
authors.affiliation: 1 Multidisciplinary Thoracic Oncology Program, Baptist Cancer Center, Memphis, TN, USA ; 2 Department of Oncology, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy ; 3 Institute of Oncology Ion Chiricuta, Cluj-Napoca, Romania ; 4 Genentech Inc., South San Francisco, CA, USA ; 5 F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Federico
authors.initials: F
authors.lastname: Cappuzzo
authors.affiliation: 1 Multidisciplinary Thoracic Oncology Program, Baptist Cancer Center, Memphis, TN, USA ; 2 Department of Oncology, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy ; 3 Institute of Oncology Ion Chiricuta, Cluj-Napoca, Romania ; 4 Genentech Inc., South San Francisco, CA, USA ; 5 F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Tudor
authors.initials: T
authors.lastname: Ciuleanu
authors.affiliation: 1 Multidisciplinary Thoracic Oncology Program, Baptist Cancer Center, Memphis, TN, USA ; 2 Department of Oncology, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy ; 3 Institute of Oncology Ion Chiricuta, Cluj-Napoca, Romania ; 4 Genentech Inc., South San Francisco, CA, USA ; 5 F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Larry
authors.initials: L
authors.lastname: Leon
authors.affiliation: 1 Multidisciplinary Thoracic Oncology Program, Baptist Cancer Center, Memphis, TN, USA ; 2 Department of Oncology, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy ; 3 Institute of Oncology Ion Chiricuta, Cluj-Napoca, Romania ; 4 Genentech Inc., South San Francisco, CA, USA ; 5 F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Klughammer
keywords: Tyrosine kinase inhibitor (TKI) therapy; lung cancer treatment; survival; targeted therapy