Randomised, placebo-controlled, double-blind, parallel-group phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer

Eur J Cancer. 2013 Aug;49(12):2633-42. doi: 10.1016/j.ejca.2013.04.002. Epub 2013 Apr 30.

Abstract

Background: This phase III study investigated the addition of aflibercept to gemcitabine, in patients with advanced pancreatic cancer.

Patients and 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%).

Conclusion: Adding aflibercept to gemcitabine did not improve OS in patients with metastatic pancreatic cancer.

Keywords: Aflibercept; Angiogenesis; Pancreatic cancer; VEGF Trap.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Neoplasm Metastasis
  • Neutropenia / chemically induced
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Proteinuria / chemically induced
  • Receptors, Vascular Endothelial Growth Factor / administration & dosage
  • Receptors, Vascular Endothelial Growth Factor / adverse effects
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / adverse effects
  • Treatment Outcome

Substances

  • Recombinant Fusion Proteins
  • Deoxycytidine
  • aflibercept
  • gemcitabine
  • Receptors, Vascular Endothelial Growth Factor