The National Institute for Health and Care Excellence (NICE), the healthcare guidance body, has today (30 March) issued draft guidance recommending the use of denosumab (Xgeva, Amgen) for certain groups of cancer patients whose disease has spread to their bones. This is now subject to public consultation before the recommendations are reviewed and final guidance is published later in the year.

NICE is currently appraising denosumab as a treatment for bone metastases from solid tumours. This is when cancer cells from a ‘solid' tumour (e.g. breast, prostate, lung or kidney) spread from their original location to the bone. The spine, pelvis, hip, upper leg bones and skull are most commonly affected by bone metastases. Symptoms include pain, and weakening and eventual destruction of the bone.

The draft guidance recommends denosumab as a treatment option for the prevention of skeletal-related events (pathological fracture, radiation to bone, spinal cord compression or surgery to bone) for:

• People with bone metastasis from breast cancer.
• People with painful bone metastasis from hormone-refractory prostate cancer for whom other treatments (including analgesics and palliative radiotherapy) have failed.
• People with bone metastasis from other solid tumours for whom zoledronic acid is indicated.

All recommendations stipulate the drug should only be prescribed 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 is associated with increased pain and skeletal-related events such as fractures and spinal cord compression. It can have a major impact on quality of life and we are therefore pleased to be able to recommend denosumab.”

Consultees, including the manufacturer, healthcare professionals and members of the public are now able to comment on the preliminary recommendations. The consultation is open until Tuesday 24 April 2012 and all feedback received during this period will be fully considered by the committee at a second meeting. Following this, the next draft of the guidance will be issued.

Until final guidance is issued to the NHS, NHS bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations across the country.

Ends

Notes to Editors

About the guidance

1. The draft guidance will be available at TA265 from Friday 30 March 2012. Please contact the NICE press office for an embargoed copy of the draft guidance.

2. Most patients with bone metastasis from breast or prostate cancer are treated with bisphosphonates (according to NICE clinical guidelines where appropriate[1]). Of these, clinical specialists told the Independent Appraisal Committee that zoledronic acid[2] and ibandronic acid (also known as ibandronate)[3] 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.

3. The appraisal committee considered denosumab as an alternative to bisphosphonates and as an alternative to best supportive care where bisphosphonates are not used. 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 slightly more clinically effective than the bisphosphonate in all three cancer groups for which there was trial evidence (breast, prostate and non-small cell lung cancer).

4. The committee heard from clinical specialists that they considered denosumab could be given in mild to moderate renal failure and this could be particularly valuable for patients with metastatic prostate cancer, many of whom have reduced renal function. The committee understood that denosumab may have a specific role in preventing skeletal related events for people who cannot be treated with bisphosphonates because of reduced renal function.

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 from non-small cell lung cancer. It also concluded that in people with bone metastases from breast and prostate cancer, denosumab was a cost-effective option as long as it was given in accordance with current NICE recommendations [4]. 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 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%.

7. The cost of one 120 mg vial of denosumab is £309.86 (excluding VAT; BNF 62). 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.

8. 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.

9. Prior to this appraisal, NICE has published the following guidance in relation to denosumab:

a. TA240: Denosumab for the prevention of osteoporotic fractures in postmenopausal women

b. TA194: Bone loss (therapy-induced) in non-metastatic prostate cancer - denosumab (terminated appraisal)

About NICE

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.