title: A phase II study of bevacizumab and erlotinib as initial treatment for metastatic non-squamous, non-small cell lung cancer with serum proteomic evaluation.
abstract: BACKGROUND
  Erlotinib alone or bevacizumab in combination with chemotherapy improve survival in patients with advanced non-small cell lung cancer. The current trial of erlotinib and bevacizumab was designed as an alternative to initial conventional chemotherapy for advanced lung cancer and a platform to explore selection factors.
  
  
  METHODS
  Eligibility criteria included stage IIIB/IV or recurrent non-squamous, non-small cell lung cancer (NSNSCLC), no prior chemotherapy for metastatic disease, PS=0-1, and no history of brain metastases for the first 40 patients. An expansion cohort of an additional 10 patients allowed treated brain metastases. Patients received erlotinib 150 mg/day and bevacizumab 15 mg/kg/3 weeks until objective or symptomatic progression. Pretreatment serum was collected for blinded VeriStrat® evaluation.
  
  
  RESULTS
  Fifty patients were accrued. The median age was 65 years, 10 were octogenarians, 37 had PS=1, 25 were female and 12 were never-smokers. Histologies were adenocarcinoma in 26 and unspecified in 24. Partial responses were observed in 12 (24%), stable in 30 (60%) and progressive disease in 8 (16%). The median time on therapy was 15.5 weeks. The median survival was 50.4 weeks with 1 and 2 years survivals of 50% and 21%, respectively. Only 38% of eligible patients received second line therapy, most often due to decline in PS. VeriStrat® analysis was performed in 42 subjects (Good 32, Poor 9, and Indeterminate 1). Significant differences based on VeriStrat® signature were noted in PFS (Good=18.9 weeks, Poor=6.3 weeks, p=0.0035) and overall survival (Good=71.4 weeks, Poor=19.9 weeks, p=0.0015).
  
  
  CONCLUSIONS
  Survival in an unselected population of patients with NSNSCLC treated with bevacizumab and erlotinib approximated that expected with conventional chemotherapy. VeriStrat® analyses distinguished patients who were likely or unlikely to benefit from this combination.
authors.affiliation: Huntsman Cancer Institute at University of Utah, UT, United States. wallace.akerley@hci.utah.edu
authors.forename: Wallace
authors.initials: W
authors.lastname: Akerley
authors.forename: Kenneth
authors.initials: K
authors.lastname: Boucher
authors.forename: Nathan
authors.initials: N
authors.lastname: Rich
authors.forename: Lyle
authors.initials: L
authors.lastname: Egbert
authors.forename: Graydon
authors.initials: G
authors.lastname: Harker
authors.forename: Julie
authors.initials: J
authors.lastname: Bylund
authors.forename: Terry
authors.initials: T
authors.lastname: Van Duren
authors.forename: Chakravarthy
authors.initials: C
authors.lastname: Reddy
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001798:Blood Proteins / Q000378:metabolism; D001932:Brain Neoplasms / Q000401:mortality / Q000517:prevention & control / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D000069347:Erlotinib Hydrochloride; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D040901:Proteomics / Q000379:methods; D011799:Quinazolines / Q000008:administration & dosage; D016019:Survival Analysis
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D001798:Blood Proteins; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride