title: Randomised, placebo-controlled, double-blind, parallel-group phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer.
abstract: BACKGROUND
  This phase III study investigated the addition of aflibercept to gemcitabine, in patients with advanced pancreatic cancer.
  
  
  METHODS
  Patients with metastatic pancreatic cancer were randomly assigned to receive either intravenous (i.v.) aflibercept, 4 mg/kg every 2 weeks, or matching placebo combined with gemcitabine, 1000 mg/m(2) i.v. weekly for 7 weeks out of 8, then weekly for 3 weeks out of 4 until progressive disease, unacceptable toxicity or withdrawal of consent. The primary objective was to demonstrate an improvement in overall survival (OS) between the treatment arms.
  
  
  RESULTS
  The study was stopped for futility following a planned interim analysis of OS in 427 randomised patients. With a median follow-up of 7.9 months, based on the 546 patients at study termination, median OS was 7.8 months in the gemcitabine plus placebo arm (n=275) versus 6.5 months in the gemcitabine plus aflibercept arm (n=271), which was not significant (hazard ratio 1.165, 95% confidence interval (CI) 0.921-1.473, p=0.2034). Median progression-free survival was 3.7 months in both arms. Treatment discontinuations due to adverse events were more frequent in the aflibercept than in the placebo-containing arm (23% versus 12%).
  
  
  CONCLUSIONS
  Adding aflibercept to gemcitabine did not improve OS in patients with metastatic pancreatic cancer.
authors: Department of Hepato-Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France. philippe.rougier@egp.aphp.fr
authors: Philippe
authors: P
authors: Rougier
authors: Hanno
authors: H
authors: Riess
authors: Robert
authors: R
authors: Manges
authors: Petr
authors: P
authors: Karasek
authors: Yves
authors: Y
authors: Humblet
authors: Carlo
authors: C
authors: Barone
authors: Armando
authors: A
authors: Santoro
authors: Sylvie
authors: S
authors: Assadourian
authors: Laurence
authors: L
authors: Hatteville
authors: Philip A
authors: PA
authors: Philip
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011507:Proteinuria / Q000139:chemically induced; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage / Q000009:adverse effects; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D011993:Recombinant Fusion Proteins; D003841:Deoxycytidine; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor; D000093542:Gemcitabine
keywords: Aflibercept; Angiogenesis; Pancreatic cancer; VEGF Trap