title: A randomized phase 2 study of erlotinib alone and in combination with bortezomib in previously treated advanced non-small cell lung cancer.
abstract: BACKGROUND
  This phase 2 study was conducted to determine the efficacy and safety of erlotinib alone and with bortezomib in patients with non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with histologically or cytologically confirmed relapsed or refractory stage IIIb/IV NSCLC were randomized (1:1; stratified by baseline histology, smoking history, sex) to receive erlotinib 150 mg/d alone (arm A; n = 25) or in combination with bortezomib 1.6 mg/m2, days 1 and 8 (arm B; n = 25) in 21-day cycles. Responses were assessed using Response Evaluation Criteria in Solid Tumors. Tumor samples were evaluated for mutations predicting response. Six additional patients received the combination in a prior dose deescalation stage and were included in safety analyses.
  
  
  RESULTS
  Response rates were 16% in arm A and 9% in arm B; disease control rates were 52 and 45%, respectively. The study was halted at the planned interim analysis due to insufficient clinical activity in arm B. Median progression-free survival and overall survival were 2.7 and 7.3 months in arm A, and 1.3 and 8.5 months in arm B. Six-month survival rates were 56.0% in both arms; 12-month rates were 40 and 30% in arms A and B, respectively. Response rate to erlotinib+/-bortezomib was significantly higher in patients with epidermal growth factor receptor mutations (50 versus 9% for wild type). The most common treatment-related grade > or =3 adverse event was skin rash (three patients in each treatment group).
  
  
  CONCLUSIONS
  Insufficient activity was seen with erlotinib plus bortezomib in patients with relapsed/refractory advanced NSCLC to warrant a phase 3 study of the combination.
authors.affiliation: Department of Hematology and Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA. thomas.lynch@yale.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lynch
authors.forename: David
authors.initials: D
authors.lastname: Fenton
authors.forename: Vera
authors.initials: V
authors.lastname: Hirsh
authors.forename: David
authors.initials: D
authors.lastname: Bodkin
authors.forename: Edward L
authors.initials: EL
authors.lastname: Middleman
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiappori
authors.forename: Balazs
authors.initials: B
authors.lastname: Halmos
authors.forename: Reyna
authors.initials: R
authors.lastname: Favis
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: William L
authors.initials: WL
authors.lastname: Trepicchio
authors.forename: Omar
authors.initials: O
authors.lastname: Eton
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011719:Pyrazines / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D011799:Quinazolines; D000069286:Bortezomib; D000069347:Erlotinib Hydrochloride