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

Philippe Rougier, Hanno Riess, Robert Manges, Petr Karasek, Yves Humblet, Carlo Barone, Armando Santoro, Sylvie Assadourian, Laurence Hatteville, Philip A. Philip

Research output: Contribution to journalArticle

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/m2 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.

Original languageEnglish
Pages (from-to)2633-2642
Number of pages10
JournalEuropean Journal of Cancer
Volume49
Issue number12
DOIs
Publication statusPublished - Aug 2013

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gemcitabine
Pancreatic Neoplasms
Placebos
Survival
Therapeutics
Medical Futility
Survival Analysis
Disease-Free Survival
aflibercept
Confidence Intervals

Keywords

  • Aflibercept
  • Angiogenesis
  • Pancreatic cancer
  • Trap
  • VEGF

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Randomised, placebo-controlled, double-blind, parallel-group phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer. / Rougier, Philippe; Riess, Hanno; Manges, Robert; Karasek, Petr; Humblet, Yves; Barone, Carlo; Santoro, Armando; Assadourian, Sylvie; Hatteville, Laurence; Philip, Philip A.

In: European Journal of Cancer, Vol. 49, No. 12, 08.2013, p. 2633-2642.

Research output: Contribution to journalArticle

Rougier, Philippe ; Riess, Hanno ; Manges, Robert ; Karasek, Petr ; Humblet, Yves ; Barone, Carlo ; Santoro, Armando ; Assadourian, Sylvie ; Hatteville, Laurence ; Philip, Philip A. / Randomised, placebo-controlled, double-blind, parallel-group phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer. In: European Journal of Cancer. 2013 ; Vol. 49, No. 12. pp. 2633-2642.
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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/m2 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.",
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AU - Rougier, Philippe

AU - Riess, Hanno

AU - Manges, Robert

AU - Karasek, Petr

AU - Humblet, Yves

AU - Barone, Carlo

AU - Santoro, Armando

AU - Assadourian, Sylvie

AU - Hatteville, Laurence

AU - Philip, Philip A.

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N2 - 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/m2 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.

AB - 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/m2 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.

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