The cost-effectiveness agency for England and Wales says that it will not recommend bevacizumab in combination with capecitabine to treat advanced metastatic breast cancer.
In new draft guidance issued April 18, the National Institute for Health and Clinical Excellence (NICE) cited insufficient evidence in support of the drug combination, one of two bevacizumab regimens licensed in the European Union for the first-line treatment of advanced metastatic breast cancer.
Roche’s bevacizumab (Avastin) is a humanized monoclonal antibody that blocks vascular endothelial growth factor, reducing blood flow to tumors. The U.S. Food and Drug Administration revoked bevacizumab’s breast cancer indications altogether in November 2011, citing an unfavorable risk-benefit ratio.
The European Medicines Agency did not follow suit, however. Bevacizumab is licensed in Europe in combination with paclitaxel and also with capecitabine, which is used when paclitaxel is judged inappropriate, for advanced metastatic breast cancer.
In February 2011, NICE rejected bevacizumab and paclitaxel for the same indication.
In announcing its decision on bevacizumab and capecitabine, NICE cited uncertainties about overall survival benefit in results from RIBBON-1, a randomized controlled trial of bevacizumab in 1,237 women with advanced breast cancer. In the capecitabine arm of the trial, 615 patients were randomized to capecitabine plus bevacizumab or capecitabine plus placebo.
Although the results showed that capecitabine and bevacizumab prolonged progression-free survival by 2.9 months compared with capecitabine monotherapy, it remained unclear whether that benefit translated into an improvement in overall survival, NICE said, because so many patients on monotherapy crossed over to bevacizumab in the trial’s open-label postprogression phase.
NICE cited in its negative guidance the fact that no quality of life data had been collected in the trial, and that serious adverse reactions were higher with bevacizumab plus capecitabine (36.6%) than with capecitabine plus placebo (22.9%). "In addition, the number of patients with hypertension, proteinuria, sensory neuropathy, and venous thromboembolic events was higher with bevacizumab plus capecitabine compared with capecitabine plus placebo," NICE said in an April 18 press statement about its decision. "The Committee concluded that bevacizumab plus capecitabine had a less favorable toxicity profile than capecitabine plus placebo."
Finally, as in all NICE decisions, there was the question of cost. The manufacturer’s best-case incremental cost-effectiveness ratio (ICER) for bevacizumab plus capecitabine was £82,000 (U.S.$131,400) per quality-adjusted life year gained, and this only for a subgroup of patients. The ICER placed bevacizumab firmly out of NICE’s cost-effectiveness range.
Bevacizumab, which is administered by intravenous infusion, is dosed at 15 mg/kg every 3 weeks, amounting, NICE said, to an average monthly cost of around £3,689 (U.S.$5,913) per patient.