INDIANAPOLIS—Adding the antiangiogenesis agent bevacizumab (Avastin) to
capecitabine (Xeloda) increases the objective response rate—but not
progression-free survival—in women with advanced breast cancer, according to a
phase III trial. This was the first randomized trial to report results with an
antiangiogenic agent in patients with metastatic disease, according to lead
investigator Kathy D. Miller, MD, assistant professor of medicine in the
division of hematology/oncology at Indiana University School of Medicine,
Indianapolis.
The trial compared capecitabine plus bevacizumab to capecitabine alone in
heavily pretreated women with metastatic breast cancer. Bevacizumab is a
humanized monoclonal antibody directed against vascular endothelial growth
factor (VEGF), a potent proangiogenic peptide. Dr. Miller said that in a phase
II trial of bevacizumab alone in similarly heavily pretreated patients, 17% of
the patients either responded or were stable at 22 weeks.
Patients Pretreated With Anthracycline and Taxane
All participants in the current study had been treated with both an
anthracycline and a taxane, and the patients generally had received one or two
previous therapies for metastatic disease. The one exception was that women who
had received adjuvant therapy with an anthracycline and a taxane but had
relapsed within 1 year were allowed to enter the trial as their first
metastatic therapy.
Patients were required to have completed their last therapy at least 21 days
before entering the trial and had to have an Eastern Cooperative Oncology Group
(ECOG) performance status of 0 or 1. In an attempt to limit potential toxicity,
patients were excluded if they had central nervous system metastases,
significant baseline proteinuria (greater than 500 mg/24 hours), or required
therapeutic anticoagulation.
A total of 462 patients were enrolled. The median age was 51, and 50% of the
participants were ECOG performance status 0. About 50% were estrogen
receptor-positive, 42% were progesterone receptor-positive, and 27% were
HER2-positive. The median time since diagnosis of metastatic disease was 1.2
years, and 76% of the patients had visceral disease.
Patients were randomized to capecitabine plus bevacizumab or capecitabine
alone. Capecitabine was given in standard doses of 1,250 mg/m2 twice
daily for 14 days in a 21-day cycle. Bevacizumab was given as a single
intravenous infusion every 3 weeks at a dose of 15 mg/kg.
