Thursday May 17 2012
Zytiga (abiraterone) could be offered to men with metastatic prostate cancer
“NHS ban on pill to treat prostate cancer is lifted,” the Daily Express has said, while the Daily Mail has warned that a “prostate cancer wonder drug” was set for approval “south of border but turned down by Scotland”. The stories focus on the fact that the prostate cancer drug abiraterone may soon be available on the NHS in certain circumstances.
These stories are based on a revised decision on draft guidance published by The National Institute for Health and Clinical Excellence (NICE), which makes recommendations about which treatments should be available on the NHS in England and Wales. It recommends that abiraterone (brand name Zytiga) be made available for the treatment of advanced prostate cancer that has not responded to chemotherapy.
Previous draft NICE guidance published in February rejected the use of abiraterone, concluding that it was not cost-effective. The new draft guidance has reconsidered this decision following an offer from the drug manufacturer to make the drug available at a lower price to the NHS.
The Scottish Medicines Consortium (SMC), which advises NHS bodies in Scotland about the status of new treatments, published guidance in March that rejected making abiraterone available. The SMC is currently considering further evidence and is due to publish further guidance this summer.
What is abiraterone used for?
Abiraterone is a type of hormone therapy for cancer that has spread beyond the prostate to other parts of the body (metastatic prostate cancer). It is a tablet taken once a day in combination with a steroid drug (prednisolone or prednisone), which reduces inflammation.
Hormone treatments for prostate cancer aim to block the production of certain male hormones (androgens) that stimulate prostate cancers to grow. Although there are already hormone treatments for prostate cancer, the new drug works in a different way by blocking cytochrome P17, an enzyme that enables the body to make androgens.
Abiraterone was licensed by the European Medicines Agency (EMA) in September 2011. After price changes made the drug more affordable, NICE guidance recommended abiraterone for use within certain circumstances. NICE said it is suitable is for men with:
- metastatic prostate cancer that has not responded to castration (either surgical where the testes are removed, or where medical treatments are used to block male hormones); and
- metastatic prostate cancer that has not responded to a chemotherapy regimen that contains docetaxel (a chemotherapy drug licensed for hormone-resistant prostate cancer)
NICE added that abiraterone should be used in combination with the anti-inflammatory drug predisnolone (or prednisone) in both these cases.
Alternative treatment options for men with metastatic prostate cancer, whose disease still progresses after treatment with docetaxel, include a drug called mitoxantrone, supportive care and re-treatment with docetaxel (which is not recommended in current NICE guidance).
How effective is it?
NICE has concluded that abiraterone is an effective second-line treatment for advanced (metastatic) prostate cancer.
Evidence for its effectiveness comes from a large randomised controlled trial carried out in 13 countries including the UK, from May 2008 to April 2009. The trial aimed to find out how well abiraterone worked for men who had already had other types of hormone therapy and chemotherapy for advanced prostate cancer.
One group of men in the trial took abiraterone once a day together with prednisolone, while the other group took a placebo plus prednisolone.
A primary analysis of the results showed that, on average, men who had abiraterone survived about four months longer than those in the placebo group (14.8 months compared with 10.9 months, hazard ratio 0.65, 95% confidence interval 0.54 to 0.77). The trial was stopped early once the benefits of the drug became clear.
The study also included analysis of a subgroup that had received one course of chemotherapy only (as opposed to more than one). It found that in this group, men who took abiraterone lived significantly longer than men who took the placebo (17.0 months compared to 11.7 months, hazard ratio 0.71, 95% confidence interval 0.60 to 0.86). NICE said that this group is likely to be treated with abiraterone in clinical practice and would have better treatment outcomes because they had less advanced disease.
Experts also told NICE that the most important benefits were extension to life and improved quality of life, including less pain and improved mental and physical health. NICE also concluded that the drug has the benefit of being in tablet form, which means patients can take it at home. It added that abiraterone is generally safe and any adverse reactions were tolerable.
Why was the drug previously turned down by NICE?
NICE had previously said that abiraterone should not be made available on the NHS because it was not cost-effective. NICE uses a measure called the quality-adjusted life year (QALY) to assess the value for money of a medical intervention. QALY is based on the number of years of life that would be added to a patient’s life, as well as the improvement in the quality of their life in that time added by any treatment. Each year of life is assigned a value.
NICE had previously said that although the drug had survival benefits, it did not feel the drug provided enough benefit to patients to justify the price the NHS was being asked to pay, even with an (undisclosed) discount on the list price then offered by the manufacturer, Janssen. It concluded that the most plausible cost per quality adjusted life year would be at least £63,000.
The list price of abiraterone is £2,930 for a 30-day supply of 120 tablets.
It also said that the drug did not meet its criteria for an end-of-life treatment as it did not consider the population for which the drug is licensed to be small.
What has changed now?
The manufacturer of abiraterone, Janssen, has offered the NHS a further undisclosed discount on the list price of the drug. Janssen also offered further information on which patients would benefit most (the subgroup who received only one course of chemotherapy), and clarified how many patients would receive the drug as an end-of-life treatment.
This has enabled NICE to conclude that the plausible cost per quality adjusted life year for this subgroup would be less than £50,000. In coming to this revised figure, NICE also took into account that abiraterone has other quality-of-life benefits, such as being an oral drug. It also meets the criteria for an end-of-life treatment which are:
- it would be used for men who would have a short life expectancy without treatment - less than 24 months
- providing treatment would provide at least three months extension to life.
Is it definitely going to be made available?
NICE will now consult with interested parties on the new draft guidance recommending abiraterone, before it makes a final decision in June. Until then, NHS bodies are advised to make decisions locally on the funding of specific treatments.