Randomized, placebo-controlled, double-blind, phase II study of axitinib plus
docetaxel versus docetaxel plus placebo in patients with metastatic breast
cancer.
Author(s): Rugo HS, Stopeck AT, Joy AA, Chan S, Verma S, Lluch A, Liau KF, Kim S, Bycott P,
Rosbrook B, Bair AH, Soulieres D.
Affiliation(s): University of California, San Francisco Helen Diller Family Comprehensive Cancer
Center, 1600 Divisadero Ave, Second Floor, Box 1710, San Francisco, CA 94115,
USA. hrugo@medicine.ucsf.edu
Publication date & source: 2011, J Clin Oncol. , 29(18):2459-65
PURPOSE: This multicenter, randomized, double-blind, phase II study assessed
safety and efficacy of axitinib plus docetaxel in metastatic breast cancer (MBC).
PATIENTS AND METHODS: Women with MBC were randomly assigned 2:1 to receive
docetaxel 80 mg/m2 once every 3 weeks plus axitinib 5 mg twice per day
(combination arm) or placebo (placebo arm), following a lead-in phase I trial.
The primary end point was time to progression (TTP).
RESULTS: In all, 168 patients were enrolled; 112 were randomly assigned to
axitinib and 56 to placebo. Median TTP was numerically longer in the combination
arm than in the placebo arm (8.1 v 7.1 months), but this difference was not
statistically significant (hazard ratio, 1.24; 95% CI, 0.82 to 1.87; one-sided P
= .156). The difference in median TTP was greatest among patients who had
received prior adjuvant chemotherapy (9.2 v 7.0 months; P = .043, prespecified
subgroup analysis). Objective response rate was higher in the combination arm
(41.1% v 23.6%; P = .011). The most common grades 3 to 4 treatment-related
adverse events (combination/placebo) included diarrhea (10.8%/0%), fatigue
(10.8%/5.4%), stomatitis (12.6%/1.8%), mucositis (9.0%/0%), asthenia (7.2%/0%),
and hypertension (4.5%/0%). Three patients in the combination arm experienced
serious thromboembolic events (one death). Febrile neutropenia was more frequent
in the combination arm (15.3% v 7.1%); rates of other hematologic toxicities were
comparable. Increased toxicity with axitinib was generally managed by dose
reduction and/or growth factor support.
CONCLUSION: The addition of axitinib to docetaxel did not improve TTP in
first-line MBC treatment. Combination therapy may be more effective in patients
previously exposed to adjuvant chemotherapy.
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