Final results of the RIBBON-2 trial show that adding bevacizumab(Drug information on bevacizumab) (Avastin) to chemotherapy does not affect overall survival in advanced breast cancer patients who have been previously treated for their metastatic disease. These results were presented at the American Society of Clinical Oncology (ASCO) Breast Cancer Symposium last Saturday.
Median overall survival was 17.8 months in the chemotherapy arm and 18.6 months in the bevacizumab experimental arm (P = .88). The 1-year overall survival rates were 69% and 71%, respectively. No major differences were seen in the subanalysis of different chemotherapies. Nor were there differences in response or survival seen for triple-negative breast cancer patients.
The trial randomized 684 patients, two to one, to either chemotherapy or chemotherapy combined with bevacizumab at either 15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks, depending on the chemotherapy regimen. Chemotherapy type was chosen by the clinician—either capecitabine(Drug information on capecitabine), a taxane, gemcitabine(Drug information on gemcitabine), or vinorelbine.
The results of the RIBBON-2 trial were originally published in the Journal of Clinical Oncology in November 2011. Combining bevacizumab with chemotherapy as a second-line treatment in patients with HER2-negative metastatic breast cancer showed an improved progression-free survival compared to patients treated only with chemotherapy. Median progression-free survival was 7.2 months in the experimental group compared to 5.1 months in the chemotherapy only arm (P = .0072) with a 10% improvement in overall response rate that was not statistically significant.
In November 2011, the US Food and Drug Administration (FDA) revoked the approval of bevacizumab as a treatment for breast cancer due to a lack of evidence that the drug slows tumor growth or increases the survival time of patients with HER2-negative metastatic breast cancer who have not been previously treated. The FDA did not believe the efficacy justified the serious and life-threatening side effects associated with the drug.
Bevacizumab was originally approved for this indication in 2008 under the FDA’s accelerated approval program on the basis of initial data from the E2100 trial showing a 52% reduction in risk of disease progression when used with paclitaxel(Drug information on paclitaxel). Subsequent trials—AVADO, and RIBBON-1—also demonstrated a progression-free survival benefit in patients not previously treated, but none of the three trials demonstrated a survival advantage.
The utility of bevacizumab in metastatic breast cancer is unclear. “It is likely that subsets of patients with metastatic breast cancer will benefit [from bevacizumab], but we have not yet defined [these patients],” said Adam Brufsky, MD, PhD, medical oncologist and professor of medicine at the University of Pittsburgh School of Medicine and the presenter of the final results of the RIBBON-2 trial at the ASCO Breast Cancer Symposium. “We continue to search for subsets of patients with breast cancer that may have an overall survival benefit to bevacizumab with systemic chemotherapy.”