The clinical effectiveness agency for England and Wales has rejected a second bevacizumab combination for metastatic breast cancer, citing the treatment’s high cost, uncertain effect on quality of life, and lack of robust evidence for overall survival improvements.
Roche’s bevacizumab (Avastin) is a monoclonal antibody that works by inhibiting vascular endothelial growth factor (VEGF). It is licensed in the European Union in combination with Roche’s capecitabine (Xeloda) for metastatic breast cancer; however, the National Institute for Health and Clinical Excellence found that the treatment did not meet its cost-effectiveness criteria. NICE’s decision was widely expected after the agency issued negative draft guidance in April.
In 2010, NICE turned down bevacizumab in combination with a taxane for first-line treatment of metastatic breast cancer, its licensed indication at the time; the European Medicines Agency late that year limited the breast cancer indication to a combination with paclitaxel.
In April 2011, EMA said bevacizumab could also be used with capecitabine if other chemotherapy treatments are inappropriate, citing evidence from RIBBON-1, a randomized, placebo-controlled trial that showed average progression-free survival of 8.6 months in patients receiving the combination, compared with 5.7 months in those receiving capecitabine alone.
In a final appraisal published July 6, NICE acknowledged the statistically significant, 2.9-month gain in progression-free survival seen with bevacizumab in the trial. However, the agency said that quality-of-life data were not captured, and while median overall survival also improved by 2.9 months, this result was not statistically significant due in part to crossover.
The manufacturer’s submission to NICE included clinical trial evidence only for a subgroup of people who had been previously treated with a taxane, while the full indication includes both previously treated and treatment-naive patients.
The NICE reviewers said they found "no biologically plausible reason why bevacizumab plus capecitabine would be more effective" in the previously treated subgroup than in the broader population for which the combination is licensed. They also concluded that the incremental cost-effectiveness ratio for the treatment would be at least £82,000 (U.S.$127,000) per quality-adjusted life year (QALY).
Bevacizumab is administered by intravenous infusion at a recommended dose of 10 mg/kg of body weight once every 2 weeks or 15 mg/kg of body weight once every 3 weeks. The average price of bevacizumab treatment for breast cancer in the United Kingdom is £3,689 (U.S.$5,727) per month, according to NICE.