title: A multicenter, phase 2 study of vascular endothelial growth factor trap (Aflibercept) in platinum- and erlotinib-resistant adenocarcinoma of the lung.
abstract: BACKGROUND
  Aflibercept (vascular endothelial growth factor [VEGF] trap), a recombinant fusion protein, blocks the activity of VEGF-A and placental growth factor and has demonstrated activity in pretreated patients with lung cancer in a phase I trial. This study evaluated the efficacy and safety of intravenous aflibercept in patients with platinum- and erlotinib-resistant lung adenocarcinoma.
  
  
  METHODS
  An open-label, single arm, multicenter trial was conducted, with the primary end point of response rate (modified RECIST). Additional endpoints included safety, duration of response, progression-free survival, and overall survival. Patients with platinum- and erlotinib-resistant lung adenocarcinoma were eligible. Aflibercept 4.0 mg/kg intravenous every 2 weeks was administered until progression of disease or intolerable toxicity.
  
  
  RESULTS
  Ninety-eight patients were enrolled; 89 were evaluable for response. Median age was 60 years, 41% were men with Eastern Cooperative Oncology Group performance status 0/1/2 in 35/55/9% of patients. The overall response rate was 2.0%, (95% confidence interval, 0.2-7.2%). Median progression-free survival was 2.7 months, and overall was survival 6.2 months. Six- and 12-month survival rates were 54 and 29%, respectively. A median of four cycles was administered (range 1-22). Common grade 3/4 toxicities included dyspnea (21%), hypertension (23%), and proteinuria (10%). Two cases of grade 5 hemoptysis were reported, and one case each of tracheoesophageal fistula, decreased cardiac ejection fraction, cerebral ischemia, and reversible posterior leukoencephalopathy.
  
  
  CONCLUSIONS
  Aflibercept has minor single agent activity in heavily pretreated lung adenocarcinoma, and is well tolerated, with no unexpected toxicities. Further studies evaluating aflibercept in lung cancer, in combination with chemotherapy and other targeted therapies, are ongoing.
authors.affiliation: Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
authors.forename: Luis E
authors.initials: LE
authors.lastname: Raez
authors.forename: Benjamin
authors.initials: B
authors.lastname: Besse
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Rosen
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlesi
authors.forename: E
authors.initials: E
authors.lastname: Massarelli
authors.forename: Nashat
authors.initials: N
authors.lastname: Gabrail
authors.forename: Lowell L
authors.initials: LL
authors.lastname: Hart
authors.forename: Kathy S
authors.initials: KS
authors.lastname: Albain
authors.forename: Lloyd
authors.initials: L
authors.lastname: Berkowitz
authors.forename: Ostap
authors.initials: O
authors.lastname: Melnyk
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.forename: Lars
authors.initials: L
authors.lastname: Sternas
authors.forename: Judie
authors.initials: J
authors.lastname: Ackerman
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Shun
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.forename: Roy S
authors.initials: RS
authors.lastname: Herbst
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D011799:Quinazolines; D011993:Recombinant Fusion Proteins; C533178:aflibercept; D000069347:Erlotinib Hydrochloride; D040262:Receptors, Vascular Endothelial Growth Factor