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
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