INDIANAPOLIS—Adding the antiangiogenesis agent bevacizumab(Drug information on bevacizumab) (Avastin) to capecitabine(Drug information on 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(Drug information on 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.
