A drug considered a breakthrough treatment for advanced melanoma has been turned down by England’s clinical and cost-effectiveness agency.
In first draft guidance issued Oct. 14, the National Institute for Health and Clinical Excellence, which makes recommendations to the National Health Service in England and Wales, said that it was not likely to recommend ipilimumab (Bristol-Myers Squibb’s Yervoy).
The agency cited cost concerns and what it called insufficient follow-up results from a manufacturer-sponsored, phase III, randomized, placebo-controlled trial of ipilimumab (n = 676). The drug, a monoclonal antibody, was shown to significantly improve overall survival in previously treated patients with unresectable stage II or IV melanomas (J. Clin. Oncol. 28:18s, 2010 [suppl; abstr 4]).
Subjects who received ipilimumab alone or with a peptide vaccine saw a median survival of about 10 months, compared with 6.4 months for those receiving only the vaccine. At 1 year follow up, between 44% and 46% of subjects in the ipilimumab arms had survived, compared with 25% in the vaccine-only arm, and at 2 years, between 22% and 24% in the ipilimumab arms had survived, compared with 14% in the vaccine-only arm.
"Ipilimumab is not a cost-effective use of NHS resources."
On the strength of these results, in patient groups for whom few effective treatments exist, the Food and Drug Administration fast-tracked its review of ipilimumab, approving it in March; the European Medicines Agency recommended it in May, and it has been available Europe-wide since July.
But NICE chief executive Andrew Dillon criticized the same results in a news release, saying that ipilimumab had not been compared to the drugs currently used to treat stage III or IV melanoma. (In U.K. practice, this is carboplatin-based chemotherapy, dacarbazine, or supportive care.)
Although the results, Mr. Dillon continued, "did show the drug could potentially be very effective for a small percentage of patients," the follow up from the trial "was too short to determine how long this effect would last."
Clinical specialists have advised NICE that about 30% of people treated with ipilimumab would have improved survival, with an estimated 10% potentially experiencing long-term benefits.
Currently no biomarkers have been established to identify patients who will benefit, Mr. Dillon said, and "ipilimumab currently costs around £80k per patient whether the treatment is effective for them or not." On the basis of evidence submitted so far, he said, "ipilimumab is not a cost-effective use of NHS resources."
NICE’s decision on ipilimumab is likely to be met with fierce criticism and appeals in the United Kingdom, where about 10,000 new cases of malignant melanoma are registered each year, a fifth of them in young adults between the ages of 15 and 39. Some 400-500 Britons with advanced melanoma have disease that has progressed on second-line treatment, NICE said. The 5-year survival rates are between 40% and 50% for stage III disease and 5%-15% for stage IV disease, where median survival is 6-9 months.
Ipilimumab is administered intravenously. It works by blocking the activity of CTLA-4, boosting and prolonging the body’s T-cell response against cancer cells. At £20k per dose, and four doses per course of treatment, NICE estimates the incremental cost effectiveness ratio for ipilimumab at between £54,000 and £70,000 per quality-adjusted life-year gained, based on current evidence.
NICE’s draft guidance on ipilimumab is open for comment until Nov. 4.