IHS Global Insight Perspective | |
Significance | The National Institute for Health and Clinical Excellence (NICE) has issued a final appraisal determination rejecting Roche's blockbuster drug Avastin. |
Implications | According to NICE, there is not sufficient evidence on the benefits of the drug relative to other treatment options to justify its high cost. |
Outlook | Roche has the option to appeal the decision, although it is highly unlikely that this will do much to change the final guidance on the drug. |
The United Kingdom's National Institute for Health and Clinical Excellence (NICE) has issued a final appraisal determination (FAD) rejecting the use of Swiss pharma major Roche's Avastin (bevacizumab) in combination with a taxane for the first-line treatment of metastatic breast cancer under the country's National Health Service (NHS). The manufacturer's cost-effectiveness analysis was based on a three-state (progression-free survival, progression, or death) Markov model that compared treatment with Avastin in combination with paclitaxel against three comparators: weekly paclitaxel, docetaxel, or gemcitabine plus three-weekly paclitaxel. The manufacturer conducted base-case analyses. The first analysis used list prices of £25,929 (US$40,758) for Avastin and £7,720 for paclitaxel, based on the NICE reference case. The second analysis used an average NHS cost for paclitaxel based on the average price paid by NHS trusts over a four-month period. A patient-access scheme (PAS) for Avastin was also incorporated, under which the NHS would cover the cost of the first 10g of the drug for each patient.
According to the results of the first analysis, incremental cost-effectiveness ratios (ICERs) for Avastin plus paclitaxel were £117,803, £115,059, and £105,777 per quality-adjusted life year (QALY) gained when compared with weekly paclitaxel, docetaxel, and gemcitabine plus paclitaxel therapy, respectively. Although the PAS was not approved by the Department of Health, the manufacturer went on to submit the results from the second analysis, which showed that Avastin plus paclitaxel has lower costs per QALY in comparison with the comparator treatment; however, the ICERs were still above £57,000 per QALY gained.
These base-case results were discarded by the evidence review group (ERG), and the manufacturer was asked to submit further analysis for two subgroups: patients who had previously received treatment with a taxane, and patients with disease that was triple negative. The original model was also adapted to reflect the progression-free survival, overall survival, time to stopping treatment, and adverse event rates of the subgroups. As well as this, gemcitabine plus paclitaxel was discarded as a comparator. According to the results, in the triple-negative subgroup, the ICER per QALY for Avastin plus paclitaxel compared with paclitaxel alone was £87,865 based on list prices for paclitaxel, and £82,469 based on the average price paid by NHS trusts for paclitaxel. For the comparison with docetaxel, the ICERs were £84,740 and £64,092. In the taxane-treated subgroup, the ICERs per QALY gained for Avastin plus paclitaxel compared with paclitaxel alone were £74,640 based on list prices for paclitaxel, and £67,714 based on average NHS prices. When compared with docetaxel, the ICER per QALY for Avastin plus paclitaxel was £73,605 based on list prices, and £57,416 based on average NHS prices.
Despite the modified analysis, the ERG noted further concerns about the results, given that the clinical data used in the analysis may have resulted in biased results, and the uncertainty surrounding the choice of statistical function used in the analysis. The ERG's exploratory analysis revealed that the most plausible ICER for Avastin plus paclitaxel compared with weekly paclitaxel is likely to be between £110,000 and £259,000 per QALY gained. For Avastin plus paclitaxel compared with docetaxel, the ICER was likely to exceed £115,000 per QALY gained. For the subgroup analysis, the committee said that the results were still not within the expectable threshold and that there were further concerns about the uncertainties associated with the estimates that meant they were not likely to be reliable. The committee also concluded that the drug did not meet end-of-life criteria under NICE guidelines. The FAD can be seen here.
Outlook and Implications
This latest NICE rebuff for Avastin in breast cancer is not unexpected, given earlier negative verdicts issued by NICE for the drug in this indication. The average monthly cost of Avastin is estimated to be £3,304.76 every two weeks at a dosage of 10 mg/kg. For the dosage of 15 mg/kg every three weeks, the cost of the drug is £3,435.70. Although this decision will be met with the usual high-profile scrutiny as to why NICE continues to reject the drug despite it being made available in other European countries, NICE stands behind its decision. According to NICE's chief executive Andrew Dillon, the agency "did not receive any evidence from the manufacturer to show that bevacizumab can significantly lengthen a patient's life or, importantly, offer a better quality of life than existing treatments". He also added that although there is evidence to suggest that the drug may inhibit cancer growth, its results varied from study to study. In addition, its effect on overall survival remains "unclear". NICE also highlighted the fact that regulatory agencies—namely the U.S. FDA and the European Medicines Agency—are indeed due to make decisions on whether or not the drug should continue to be approved in the breast cancer setting, and that this decision will affect future appraisals of the drug. This FAD is by no means final, and Roche will be able to launch an appeal. Avastin has also been rejected for used in metastatic colorectal cancer and renal cell carcinoma (see United Kingdom: 12 November 2010: NICE Rejects Avastin for mCRC in FAD).