RIBBON-2: A Randomized, Double-Blind, Placebo-Controlled, Phase III Trial Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy for Second-Line Treatment of Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Full Text
Journal of Clinical Oncology, 10/14/2011
Clinical Article
Brufsky AM et al. – The combination of bevacizumab with commonly used chemotherapies improved PFS in the second-line treatment of patients with HER2-negative metastatic breast cancer, with a safety profile comparable with that in prior phase III studies
Methods- Patients were randomly assigned 2:1 to chemotherapy + bevacizumab or to chemotherapy + placebo
- Before random assignment, investigators chose capecitabine, a taxane (paclitaxel, nab-paclitaxel, or docetaxel), gemcitabine, or vinorelbine
- Dosing for bevacizumab or placebo was 15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks, depending on chemotherapy regimen
- Primary end point was PFS
- Secondary end points included OS, PFS by chemotherapy cohort, ORR, duration of objective response, 1-year survival rate, and safety
- RIBBON-2 enrolled 684 patients (225, chemotherapy + placebo; 459, chemotherapy + bevacizumab)
- Combination of bevacizumab with chemotherapy demonstrated statistically significant benefit
- Median PFS increased from 5.1 to 7.2 months (stratified hazard ratio for PFS, 0.78; 95% CI, 0.64 to 0.93; P = .0072)
- 10% improvement in ORR between placebo- and bevacizumab-containing arms (39.5% v 29.6%; P = .0193), although not statistically significant, was consistent with previous trials
- No statistically significant difference in overall survival
- Most common grade ≥ 3 AEs related to bevacizumab treatment were hypertension (9.0%) and proteinuria (3.1%)
- Increased number of AEs leading to study discontinuation in chemotherapy + bevacizumab arm compared with the chemotherapy + placebo arm (13.3% v 7.2%)
