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Invest New Drugs (2013) 31:13451354 DOI 10.1007/s10637-013-9991-2
PHASE II STUDIES
Cediranib in combination with fulvestrantin 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 Klein
Received: 15 May 2013 /Accepted: 12 June 2013 /Published online: 26 June 2013 # Springer Science+Business Media New York 2013
Summary 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.
Presented in part at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, Texas, USA, 913 December 2009.
D. M. HyamsDesert Regional Medical Center Comprehensive Cancer Center, Palm Springs, CA, USA
A. ChanMount Medical Centre, Perth, WA, Australia
C. de OliveiraInstituto Brasileiro de Controle do Cncer, So Paulo, Brazil
R. Snyder
St Vincents Hospital, Fitzroy, VIC, Australia
J. VinholesClinionco-Unidade de Novos Tratamentos,...