Cancer Drugs: NICE Rejects Costly Treatments
The floodgate has opened for molecularly targeted antitumor agents, and with each novel compound the cost of treating cancer soars ever higher. Approval by the US Food and Drug Administration (FDA) is usually based on a delay in disease progression, but just a 2-month benefit may be statistically significant in large randomized phase 3 trials. In contrast, the United Kingdom’s National Health Service (NHS) and its advisory branch, the National Institute for Health and Clinical Excellence (NICE), have been less supportive of their use.
NICE provides guidance to the NHS on the effective use of ever-limited resources. In the past year or so, it has recommended against approval (although some decisions are preliminary and still open to appeal; see www. nice.org.uk) of the following targeted agents, which have received FDA approval in the United States:
- Sorafenib (Nexavar) for the treatment of advanced hepatocellular carcinoma, stating “its high cost could not be justified by its marginal benefit.” Trial evidence showed that sorafenib increases survival by an average of 2.8 months, but at a cost of £27,000 per patient
- Lapatinib (Tykerb) in combination with capecitabine (Xeloda) for advanced or metastatic HER2-positive breast cancer outside of clinical trials. Although GlaxoSmithKline has offered the drug free for the first 12 weeks of treatment, NICE said that lapatinib “did not represent good value for the money when compared with the alternative, currently available treatment.” Lapatinib plus capecitabine costs approximately £25,207 annually
- Bevacizumab (Avastin) in combination with a taxane for advanced breast cancer. The committee members noted that although bevacizumab delays progression by 5.5 months over paclitaxel alone, they thought that an additional 1.7 months in overall survival (OS) is not clinically meaningful. Their report stated, “When bearing in mind the uncertainties over survival rates and quality-of-life data, the committee concluded that the cost of bevacizu mab is too high for the limited and uncertain benefit it may offer patients.” NICE determined the incremental cost-effectiveness ratio (ICER) for bevacizumab plus a taxane is £115,000 to £259,000 per quality-adjusted life-year (QALY) gained
- Erlotinib (Tarceva) for maintenance treatment of advanced non– small-cell lung cancer after completion of first-line therapy. “Erlotinib has been shown to have some clinical benefit, with the manufacturer estimating it can potentially extend life by approximately 3.3 months, however, our independent advisory committee felt…the overall cost of erlotinib had been underestimated…and the cost of the drug related to the benefits it brings means that erlotinib would not be a good use of NHS money,” the committee maintained. The ICER was estimated to exceed £59,000 per QALY gained
- Ofatumumab (Arzerra) for chronic lymphocytic leukemia that is refractory to fludarabine and alemtuzumab. The appraisal committee concluded that the data, which are centered on interim results from a small subgroup of patients in an ongoing clinical trial, was not robust enough to show an OS benefit over best supportive care. “This uncertainty, combined with the additional cost of ofatumumab… meant the committee could not recommend the drug as an efficient use of NHS resources,” the report stated. The drug costs £182 per 100-mg vial, and the ICERs were figured at >£81,500 per QALY
- Everolimus (Afinitor) for the second line treatment of advanced renal cell carcinoma. “Even with the patient access scheme incorporated (first treatment free to the NHS and subsequent treatments discounted), the additional weight that would need to be assigned to the QALY benefits would be too great to fall within the range currently considered cost-effective,” the report stated. Cost-effectiveness was estimated at £58,300 per QALY.