Investigational New Drugs

, Volume 31, Issue 5, pp 1345–1354 | Cite as

Cediranib in combination with fulvestrant in hormone-sensitive metastatic breast cancer: a randomized Phase II study

  • David M. Hyams
  • Arlene Chan
  • Celia de Oliveira
  • Raymond Snyder
  • Jeferson Vinholes
  • M. William Audeh
  • Victor M. Alencar
  • Janine Lombard
  • Bijoyesh Mookerjee
  • John Xu
  • Kathryn Brown
  • Paula KleinEmail author


Hormone receptor-positive breast cancer is treated with estrogen inhibitors. Fulvestrant (FASLODEX™), an estrogen receptor (ER) antagonist with no known agonist effects, competitively binds, blocks and degrades the ER. Vascular endothelial growth factor (VEGF) may mediate resistance to ER antagonists. Cediranib is a highly potent VEGF signaling inhibitor with activity against all three VEGF receptors. This randomized Phase II study evaluated cediranib plus fulvestrant. Postmenopausal women with hormone-sensitive metastatic breast cancer were eligible. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), duration of response, clinical benefit rate (CBR), safety/tolerability and pharmacokinetics (PK). Patients received cediranib 45 mg/day (n = 31) or placebo (n = 31) both plus fulvestrant. Demographic/baseline characteristics were well balanced. Patients treated with cediranib had a numerical advantage in PFS (hazard ratio = 0.867, P = 0.669; median 223 vs. 112 days, respectively) and ORR (22 vs. 8 %, respectively) vs. placebo, although not statistically significant. CBR was 42 % in both arms. The most common adverse events (AEs) in the cediranib arm were diarrhea (68 %), fatigue (61 %) and hypertension (55 %). The incidence of grade ≥3 AEs (68 % vs. 32 %), serious AEs (48 % vs. 13 %), discontinuation AEs (39 % vs. 10 %), and cediranib dose reductions/interruptions (74 % vs. 32 %) were higher in the cediranib arm. There was no evidence of a clinically relevant effect of cediranib on fulvestrant PK. Cediranib plus fulvestrant may demonstrate clinical activity in this population, but cediranib 45 mg was not sufficiently well tolerated. Investigation of lower doses of cediranib plus hormonal/chemotherapy could be considered.


Hormone-sensitive Breast cancer Cediranib Fulvestrant 



Funding for this study was provided by AstraZeneca. We thank Dr Helen Jones, from Mudskipper Bioscience, who provided medical writing assistance funded by AstraZeneca.

Conflicts of interest

D.M.H. has received research funding from AstraZeneca, consulting income and honoraria from Genomic Health, research funding and honoraria from Centocor Ortho Biotec, and honoraria from Genentech. P.K. received remuneration for an advisory board for Genentech. J.V. was a member of an AstraZeneca advisory board. M.W.A. has received consultancy fees and research funding from AstraZeneca. J.L. received honoraria from AstraZeneca. B.M. was employed by AstraZeneca and owns stock in the company. J.X. and K.B. are employees of AstraZeneca and own stock in the company. All other authors declared no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • David M. Hyams
    • 1
  • Arlene Chan
    • 2
  • Celia de Oliveira
    • 3
  • Raymond Snyder
    • 4
  • Jeferson Vinholes
    • 5
  • M. William Audeh
    • 6
  • Victor M. Alencar
    • 7
  • Janine Lombard
    • 8
  • Bijoyesh Mookerjee
    • 9
    • 12
  • John Xu
    • 9
  • Kathryn Brown
    • 10
  • Paula Klein
    • 11
    Email author
  1. 1.Desert Regional Medical Center Comprehensive Cancer CenterPalm SpringsUSA
  2. 2.Mount Medical CentrePerthAustralia
  3. 3.Instituto Brasileiro de Controle do CâncerSão PauloBrazil
  4. 4.St Vincent’s HospitalFitzroyAustralia
  5. 5.Clinionco-Unidade de Novos TratamentosPorto AlegreBrazil
  6. 6.Cedars-Sinai Outpatient Cancer CenterLos AngelesUSA
  7. 7.Centro Regional Integrado de OncologiaFortalezaBrazil
  8. 8.Newcastle Mater Misericordiae HospitalNewcastleAustralia
  9. 9.AstraZenecaWilmingtonUSA
  10. 10.AstraZenecaMacclesfieldUK
  11. 11.Beth Israel Medical Center and Continuum Cancer Centers of New YorkNew YorkUSA
  12. 12.IncyteWilmingtonUSA

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