NICE continues to recommend denosumab for most cancer patients with bone metastases
The National Institute for Health and Care Excellence (NICE) has today (17 August) published final draft guidance recommending denosumab (XGEVA, Amgen) as a treatment for people with bone metastases from most solid cancer tumours.
Bone metastases occur when the cancer spreads from its original tumour site (e.g. breast, lung or kidney) to the bone. This can weaken bones and ultimately lead to ‘skeletal-related events' such as pathological fractures, spinal cord compression, or the need for radiation or surgery to the bone. Denosumab is licensed to prevent skeletal-related events from occurring and is being appraised as such, not as an anticancer or pain relief treatment.
The draft guidance published today has been produced after a review of available evidence and two stages of public consultation. It provisionally recommends denosumab for the prevention of skeletal-related events in:
- people with bone metastases from breast cancer and
- people with bone metastases from solid tumours (other than breast or prostate) who would otherwise be prescribed bisphosphonates[a].
The draft guidance also stipulates that denosumab should be prescribed to these patients if the manufacturer provides denosumab at the discounted rate agreed with the Department of Health as part of a patient access scheme.
Professor Carole Longson, Director of the Centre for Health Technology Evaluation at NICE, said: “Bone metastasis can severely affect a person's quality of life, stopping them from doing things so many of us take for granted. We are therefore pleased that our draft guidance recommends denosumab for those patients who are most likely to benefit from the treatment.”
There is now an opportunity for consultees to request a factual change to the draft guidance or to lodge an appeal against the recommendations if they believe there are reasonable grounds to do so (the criteria for which are explained on the NICE website). If no appeals are submitted, the guidance will be published later this year and the NHS will then have a legal obligation to begin funding the treatment for eligible patients. However, until final guidance is issued, NHS bodies should make decisions locally on the funding of specific treatments.
Notes to Editors
About the guidance
1. The draft guidance will be available at http://guidance.nice.org.uk/TA/Wave21/6 from Friday 17 August 2012. Please contact the NICE press office for an embargoed copy of the draft guidance.
2. The evidence submitted for this appraisal focused on three specific ‘categories': bone metastases from breast cancer, bone metastases from prostate cancer and bone metastases from solid tumours other than breast or prostate (e.g. lung or kidney cancer). The appraisal committee considered denosumab as an alternative to a group of bone strengthening treatments called bisphosphonates[b] and as an alternative to best supportive care where bisphosphonates are not used.
3. Most patients with bone metastasis from breast or prostate cancer are treated with bisphosphonates (according to NICE clinical guidelines where appropriate[c]). Of these, clinical specialists told the Independent Appraisal Committee that zoledronic acid and ibandronic acid (also known as ibandronate) are more commonly prescribed for people with bone metastasis from breast cancer. For people with bone metastasis from prostate cancer, there is greater variation in treatment with bisphosphonates than in people with metastatic breast cancer. Some would receive zoledronic acid, usually after the disease had not responded to other treatments. There is uncertainty about the treatments in routine use for people with bone metastases from solid tumours other than breast and prostate but the committee was satisfied that bisphosphonates would be used for a proportion of people and, based on the evidence of the manufacturer it is unlikely that bisphosphonates would be used as a first-line treatment.
4. The committee noted that the clinical trials that directly compared denosumab with the bisphosphonate, zoledronic acid, consistently showed that denosumab improved skeletal-related event outcomes compared with zoledronic acid. The committee noted there were no benefits to overall survival for denosumab in comparison with zoledronic acid and although denosumab did appear to be more effective in managing pain, this was not statistically significant. However, the committee concluded that the evidence directly comparing denosumab with zoledronic acid suggested denosumab was clinically more effective than the bisphosphonate in all three cancer groups for which there was trial evidence (breast, prostate and other solid tumours).
5. The appraisal committee concluded that denosumab, based on current prices and with the patient access scheme (whereby denosumab is made available to the NHS at a discounted rate), was shown to be a cost-effective option in people who would be treated with zoledronic acid (or other bisphosphonates in the case of metastatic breast cancer). For patients with bone metastasis from solid tumours other than breast and prostate, the patient access scheme reduced the Incremental Cost Effectiveness Ratio (ICER) for denosumab compared with zoledronic acid to less than £16,000 per QALY gained and to less than £6,000 per QALY gained for patients with bone metastasis in the non-small cell lung cancer subgroup. It also concluded that in people with bone metastases from breast cancer, denosumab was a cost-effective option as long as it was given in accordance with current NICE recommendations [d]. In comparison with best supportive care, and even with the patient access scheme in place, denosumab was associated with high ICERs, the lowest of which remained above £70,000 per QALY gained. Therefore, denosumab could not be considered cost-effective when compared with best supportive care.
6. The first draft of guidance compared denosumab with bisphosphonates for all people with bone metastases from solid tumours. However, during the first consultation on this appraisal, comments from clinical experts provided the Appraisal Committee with more information on current UK clinical practice. The committee agreed that bisphosphonates should not be used as the comparator for denosumab in people with bone metastases from prostate cancer. This is because, according to NICE guidelines[e], bisphosphonates are recommended as a treatment for pain relief (a use which denosumab is not licensed for) and not to prevent skeletal-related events. Therefore, the Appraisal Committee concluded that the main comparator for this group of patients should be best supportive care. Data submitted during the second consultation on this draft guidance suggested that bisphosphonates are prescribed for people with bone metastases from prostate cancer but the committee noted a wide variety of reasons for their use. The committee concluded that the data was not robust and there should continue to be regard for the recommendations included in the NICE guideline on prostate cancer. The committee concluded that best supportive care should remain the comparator.
7. The Appraisal Committee agreed that bisphosphonates should continue to be considered as the comparator for denosumab in people with bone metastases from breast cancer and also for people with bone metastases from solid tumours other than breast or prostate who would otherwise be treated with bisphosphonates. With this in mind and when evaluating the evidence, denosumab was deemed cost-effective for these two main groups of people. The draft guidance does not recommend denosumab for people with bone metastases from prostate cancer or for the general population of people with bone metastases from solid tumours other than breast or prostate. This is because the treatment was not deemed cost effective when compared with best supportive care.
8. Following a second consultation on the draft recommendations, the committee received comments relating to pain relief being an implicit part of the prevention of skeletal-related events. The committee recognised that there would be an overlap between pain relief and the delay of such events but noted differences between treatment aims to relieve pain, prevent pain and delay worsening pain. Because the committee must make recommendations in accordance with the wording of the treatment's marketing authorisation, the committee was unable to make recommendations specifically for the use of denosumab for pain relief in people with prostate cancer. Therefore, the recommendation for people with bone metastases from prostate cancer could not be changed.
9. The manufacturer estimates there are over 150,000 patients in the UK with solid tumours and bone metastases, of which breast and prostate cancer account for more than 80%. In patients with breast cancer, approximately 0.5% will have bone metastases at diagnosis, while 4.7% will develop bone metastases within five years. Breast cancer patients with bone metastases have an average life-expectancy of approximately two years. The manufacturer's submission also reports that 11% of patients with prostate cancer also have bone metastases at the time of diagnosis. For men with prostate cancer, the presence of bone metastases reduces five-year survival from 56% to 3%.
10. The cost of a 120 mg vial of denosumab is £309.86 (excluding VAT; BNF 63). A year of treatment (13 doses) would cost £4,028.18 (excluding VAT). Costs may vary in different settings because of negotiated procurement discounts. However, the manufacturer and the Department of Health have agreed a Patient Access Scheme (PAS) whereby denosumab would be made available to the NHS at a discounted rate. The level of discount is commercial-in-confidence.
11. The Scottish Medicines Consortium (SMC) published guidance in December 2011 not recommending the use of denosumab for the prevention of skeletal related events in adults with bone metastases from solid tumours.
12. Prior to this appraisal, NICE has published the following guidance in relation to denosumab:
1. The National Institute for Health and Care Excellence (NICE) is the independent organisation responsible for providing national guidance and standards on the promotion of good health and the prevention and treatment of ill health
2. NICE produces guidance in three areas of health:
- public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector
- health technologies - guidance on the use of new and existing medicines, treatments, medical technologies (including devices and diagnostics) and procedures within the NHS
- clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.
3. NICE produces standards for patient care:
- quality standards - these reflect the very best in high quality patient care, to help healthcare practitioners and commissioners of care deliver excellent services
- Quality and Outcomes Framework - NICE develops the clinical and health improvement indicators in the QOF, the Department of Health scheme which rewards GPs for how well they care for patients
4. NICE provides advice and support on putting NICE guidance and standards into practice through its implementation programme, and it collates and accredits high quality health guidance, research and information to help health professionals deliver the best patient care through NHS Evidence.
[a] The recommendation wording ‘if bisphosphonates would otherwise be prescribed' is not intended to exclude adults who would be advised against taking bisphosphonates because of medical reasons (medical contra-indications). Patients with medical contra-indications to disallow bisphosphonates but not denosumab (e.g. renal impairment) would be able to receive denosumab.
[b] Zoledronic acid is the only bisphosphonate to have a marketing authorisation for the prevention of skeletal-related events in patients with bone metastasis from any solid tumour. Ibandronic acid is licensed as a treatment for breast cancer patients with bone metastasis only. The bisphosphonates disodium pamidronate and sodium clodronate have a marketing authorisation for breast cancer and multiple myeloma.
This page was last updated: 02 October 2012