title: A randomized, phase II, biomarker-selected study comparing erlotinib to erlotinib intercalated with chemotherapy in first-line therapy for advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  Erlotinib prolongs survival in patients with advanced non-small-cell lung cancer (NSCLC). We report the results of a randomized, phase II study of erlotinib alone or intercalated with chemotherapy (CT + erlotinib) in chemotherapy-naïve patients with advanced NSCLC who were positive for epidermal growth factor receptor (EGFR) protein expression and/or with high EGFR gene copy number.
  
  
  METHODS
  A total of 143 patients were randomly assigned to either erlotinib 150 mg daily orally until disease progression (PD) occurred or to chemotherapy with paclitaxel 200 mg/m(2) intravenously (IV) and carboplatin dosed by creatinine clearance (AUC 6) IV on day 1 intercalated with erlotinib 150 mg orally on days 2 through 15 every 3 weeks for four cycles followed by erlotinib 150 mg orally until PD occurred (CT + erlotinib). The primary end point was 6-month progression-free survival (PFS); secondary end points included response rate, PFS, and survival. EGFR, KRAS mutation, EGFR fluorescent in situ hybridization and immunohistochemistry, and E-cadherin and vimentin protein levels were also assessed.
  
  
  RESULTS
  Six-month PFS rates were 26% and 31% for the two arms (CT + erlotinib and erlotinib alone, respectively). Both were less than the historical control of 45% (P = .001 and P = .011, respectively). Median PFS times were 4.57 and 2.69 months, respectively. Patients with tumors harboring EGFR activating mutations fared better on erlotinib alone (median PFS, 18.2 months v 4.9 months for CT + erlotinib).
  
  
  CONCLUSIONS
  The feasibility of a multicenter biomarker-driven study was demonstrated, but neither treatment arms exceeded historical controls. This study does not support combined chemotherapy and erlotinib in first-line treatment of EGFR-selected advanced NSCLC, and the patients with tumors harboring EGFR mutations had a better outcome on erlotinib alone.
authors.affiliation: University of Colorado Cancer Center, 12801 E 17th Ave, Aurora, CO 80045, USA.
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
authors.forename: Fairooz
authors.initials: F
authors.lastname: Kabbinavar
authors.forename: Tim
authors.initials: T
authors.lastname: Eisen
authors.forename: Renato
authors.initials: R
authors.lastname: Martins
authors.forename: Fredrick M
authors.initials: FM
authors.lastname: Schnell
authors.forename: Rafal
authors.initials: R
authors.lastname: Dziadziuszko
authors.forename: Katherine
authors.initials: K
authors.lastname: Richardson
authors.forename: Frank
authors.initials: F
authors.lastname: Richardson
authors.forename: Bret
authors.initials: B
authors.lastname: Wacker
authors.forename: David W
authors.initials: DW
authors.lastname: Sternberg
authors.forename: Jason
authors.initials: J
authors.lastname: Rusk
authors.forename: Wilbur A
authors.initials: WA
authors.lastname: Franklin
authors.forename: Marileila
authors.initials: M
authors.lastname: Varella-Garcia
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bunn
authors.forename: Ross
authors.initials: R
authors.lastname: Camidge
authors.forename: D Ross
authors.initials: DR
authors.lastname: Camidge
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological; D015820:Cadherins / Q000378:metabolism; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D014746:Vimentin / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: D054316:Biomarkers, Pharmacological; D015820:Cadherins; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D014746:Vimentin; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D017239:Paclitaxel