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

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