Bevacizumab, docetaxel combination is effective first-line treatment for metastatic breast cancer

Phase 3 trial results show that adding bevacizumab to docetaxel as first-line therapy for newly diagnosed HER2-negative, locally recurrent, or metastatic breast cancer resulted in significantly less disease progression. "This shows that the antiangiogenic approach to treating breast cancer is effective, regardless of which taxane drug it is combined with," said lead author David Miles, MD, professor, Mount Vernon Cancer Center, Middlesex, UK. These results were presented at the 2008 American Society of Clinical Oncology (ASCO) 2008 Annual Meeting. Previous studies have shown that the combination of bevacizumab with paclitaxel doubled progression-free survival among patients with metastatic breast cancer.

In the AVADO trial, 736 previously untreated women with locally recurrent or metastatic breast cancer were randomized to receive docetaxel 100 mg/m² plus placebo every 3 weeks, or 7.5 mg/kg or 15 mg/kg every 3 weeks until disease progression occurred. All patients were subsequently given the option to receive bevacizumab treatment with second-line chemotherapy. Dr. Miles said that the 15-mg/kg dose of bevacizumab was established in previous breast cancer trials; the lower dose has been used to treat colorectal cancer.

After 11 months' follow up, tumor shrinkage was documented in 44.4% of placebo patients who responded, compared with 55.2% of patients in the low-dose bevacizumab group (p=.0295) and 63.1% in the higher dose group (p = 0.0001). Patients receiving low-dose bevacizumab were 21% less likely to have disease progression, as were 28% of those in the high-dose group.

Dr. Miles said there were no new safety signals related to bavacizumab detected during the trial. Patients receiving bevacizumab, however, had a slightly higher rate of severe side effects, which were seen in 74.8% of the high-dose group, 74.1% of the low-dose group, and 67% of the placebo group. The most common side effect was high blood pressure, which was treatable with medication. Bevacizumab has previously been associated with severe bowel perforation, but the incidence in AVADO was low, with this event occurring in two placebo patients and one patient each in the low- and high-dose bevacizumab groups.

The overall survival data from AVADA are not available because of the short follow up time, Dr. Miles said.