NICE has issued final draft guidance recommending enzalutamide (marketed as Xtandi by Astellas Pharma) for prostate cancer which has spread in people whose first treatment has failed, who have no or mild symptoms, and for whom chemotherapy is not yet clinically indicated.
The Appraisal Committee concluded that enzalutamide is a well-tolerated treatment that delays chemotherapy (which it recognised as being valuable to patients) and improves survival. It was also found to be cost-effective.
The final draft guidance for enzalutamide is now with consultees, who have the opportunity to appeal against it. Until NICE issues final guidance, NHS bodies should make decisions locally on the funding of specific treatments.
NICE is also consulting on preliminary recommendations that do not support the use of abiraterone (marketed as Zytiga by Janssen) for the same place in the treatment pathway, that is for prostate cancer which has spread in people whose first treatment has failed, who have no or mild symptoms, and for whom chemotherapy is not yet clinically indicated. The Appraisal Committee recognised that abiraterone is a well-tolerated treatment , which delayed chemotherapy but it was not convinced that the uncertain evidence for the long-term benefit of abiraterone justified accepting estimates of cost-effectiveness that were significantly above what it would normally consider acceptable.
Consultees, including the company, healthcare professionals and members of the public are now able to comment on the preliminary recommendations for abiraterone which are available for public consultation. Comments received during this consultation will be fully considered by the Committee.
Commenting on the draft guidance, Sir Andrew Dillon, NICE chief executive, said: “In this final draft guidance we recommend enzalutamide as a treatment for patients whose prostate cancer has relapsed, but for whom chemotherapy is not yet clinically indicated. There are very few treatments available for patients at this stage of prostate cancer, so this is very good news.”
“The evidence submitted for abiraterone was uncertain in terms of the extent of the quality of life and survival benefit. In addition, its current cost does not appear to justify its advantages, to patients, over current standard treatment. It is obviously disappointing not to be able to recommend at this point.”
Notes to Editors
Explanation of terms
- Enzalutamide is recommended, within its marketing authorisation, as an option for treating metastatic hormone-relapsed prostate cancer in people who have no or mild symptoms after androgen deprivation therapy has failed, and before chemotherapy is indicated, and only when the company provides it with the discount agreed in the patient access scheme
- Abiraterone is provisionally not recommended within its marketing authorisation for treating metastatic hormone-relapsed prostate cancer in people who have no or mild symptoms after androgen deprivation therapy has failed and in whom chemotherapy is not yet clinically indicated.
About the draft guidance
- The Committee heard from clinical specialists that, when cytotoxic chemotherapy is indicated, most people would have docetaxel. But, when people have no or mild symptoms, to delay chemotherapy and its adverse effects, clinicians may instead offer best supportive care including corticosteroids such as prednisolone or dexamethasone.
- The Committee concluded that enzalutamide compared with placebo extended the time to progression, but how much it extended life was uncertain because, in the trial, life extending treatments were used later on in the treatment pathway that would not be available in the NHS.
- The cost per QALY (Quality Adjusted Life Year) gained estimated by the company was £27,000. The ERG presented an ‘exploratory base case’ of £31,600 per QALY gained. The ERG and company base cases accounted for the effect of treatments received later on in the treatment pathway that would not be available in the NHS, using the IPCW method. The ERG explored a different method to account for this (2-stage method) which resulted in an ICER of £34,500.
- The Committee agreed that, between the methods used to account for treatments that would not be available in the NHS, the IPCW method applied fewer assumptions and was more plausible. The Committee agreed that enzalutamide was innovative, and recognised that there were benefits that were not captured in the modelling, such as the value to patients in delaying chemotherapy, that would reduce the ICER to a level that would be considered cost effective.
- Enzalutamide costs £2734.67 for 1 pack of 112 x 40 mg capsules. The manufacturer of enzalutamide has agreed a patient access scheme with the Department of Health. This scheme provides a simple discount to the price listed above, with the discount applied at the point of purchase or invoice. The level of the discount is commercial in confidence.
- The Committee concluded that abiraterone compared with placebo extended the time to progression, but it how much it extended life was uncertain.
- The cost per QALY gained estimated by the company was £28,600. The ERG presented an ‘exploratory base case’ of £35,500 per QALY gained. Additional ERG sensitivity analyses to explore the uncertainty of the long term benefits of abiraterone, and to use the intention to treat population in the model, resulted in ICERs of up to £59,600 per QALY gained.
- The Committee did not feel the company’s base case of £28,600 was plausible for 2 main reasons. Firstly, because it was likely to overestimate survival and quality of life gain with abiraterone. Secondly because it was based on a population that was selected for having covariate data, rather than using the full trial population.
- The Committee considered the ICER for abiraterone compared with best supportive care was between £35,500 and £59,600. The Committee agreed that abiraterone was innovative, and recognized that there were benefits that were not captured in the modelling, such as the value to patients in delaying chemotherapy. However, even taking into account these benefits the cost-effectiveness estimates were above the range considered an acceptable use of NHS resources.
- The list price of abiraterone is £2930 for 120 tablets (excluding VAT; British national formulary [BNF], accessed online November 2015). In its submission, the company proposed to reduce the list price to £2300 for 120 tablets, if abiraterone was recommended for this indication. The company also proposed a complex patient access scheme for which the NHS would pay the new list price for abiraterone for the first 10 months of treatment. After 10 months, the Company would rebate the cost of any subsequent tablets prescribed. The Committee recognished that this patient access scheme meant the cost of abiraterone to the NHS was relatively certain.
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