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NICE opens second consultation on treatment for bone metastases in some cancer patients

A second consultation is being launched today (12 June) by the National Institute for Health and Care Excellence (NICE) due to changes to draft recommendations concerning denosumab (XGEVA, Amgen) as a treatment to prevent skeletal-related events in cancer patients whose disease has spread from a solid tumour site (e.g. breast, prostate or lung) to their bones. This is known as bone metastases.

Professor Carole Longson, Director of the Centre for Health Technology Evaluation at NICE, said: “Following a consultation on the first draft of this guidance, we received very helpful comments from clinical experts that shed new light on the original draft recommendations. In particular, the consultation feedback provided the Appraisal Committee with more information on current UK clinical practice concerning the comparators in this appraisal. As a result, the committee reconsidered the evidence and revised the draft guidance. We are now welcoming comments from stakeholders on this revised draft.”

The NICE appraisal of denosumab as a treatment to delay or prevent skeletal-related events (such as pathological fractures, spinal cord compression, or radiation or surgery to the bone) in people with bone metastases from solid tumours is considering the drug as an alternative to a group of bone strengthening medicines called bisphosphonates (where they are prescribed in clinical practice) and as an alternative to best supportive care where bisphosphonates are not used.

Following the Appraisal Committee's reconsideration of evidence in light of further information received about the use of these comparators, the latest draft guidance recommends denosumab:

  • For adults with bone metastases from breast cancer
  • For adults with bone metastases from solid tumours other than breast and prostate only if zoledronic acid or disodium pamidronate would otherwise be prescribed for these patients.

Where denosumab is recommended, the draft guidance stipulates that the drug should only be prescribed if the manufacturer provides denosumab at the discounted rate agreed with the Department of Health as part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. The draft guidance does not recommend denosumab as an option for preventing skeletal-related events in adults with bone metastases from prostate cancer.

NICE and the Appraisal Committee now welcome comments on this latest version of draft guidance. Once this period of consultation ends, the committee will meet again to discuss the next stage of guidance development. Until final guidance is issued, 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 from Tuesday 12 June 2012. Please contact the NICE press office for an embargoed copy of the draft guidance.

2. Bone metastases are associated with a reduced quality of life and an increased risk of complications arising from bone weakness or disrupted calcium homeostasis (when the body is unable to maintain adequate calcium levels). These complications (such as pathological fractures, spinal cord compression, or radiation or surgery to the bone) are collectively defined as skeletal-related events. The manufacturer estimates there are over 150,000 patients in the UK with solid tumours and bone metastases.

3. Most patients with bone metastases from breast cancer and some patients with bone metastases from other tumours 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 metastases from breast cancer.

4. According to other relevant NICE guidelines;

a. The use of bisphosphonates as a treatment to prevent or reduce complications of bone metastases in men with hormone refractory prostate cancer is not recommended. In this patient group, bisphosphonates for pain relief may be considered when other treatments including analgesics and palliative radiotherapy have failed. The oral or intravenous route of administration should be chosen according to convenience, tolerability and cost[4].

b. In people with lung cancer with bone metastases that need palliation and for whom standard analgesic treatments are inadequate, single-fraction radiotherapy is recommended[5].

c. Bisphosphonates are recommended in people with breast cancer or multiple myeloma with vertebral involvement to reduce pain and the risk of vertebral fracture/collapse. In people with vertebral involvement from prostate cancer bisphosphonates are recommended only if conventional analgesia fails to control pain[6]

5. 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).

6. Following comments from clinical experts received during the first consultation of this draft guidance, the Appraisal Committee heard from the Chair of the Guideline Development Group (GDG) who developed the clinical guideline on the diagnosis and treatment of prostate cancer (and who is now the Director of the Centre for Clinical Practice at NICE). He told the committee that, during the development of the guideline, bisphosphonates were considered as a treatment to prevent skeletal-related events but ultimately were not recommended for this use. The committee heard that the intention of the NICE clinical guideline was to recommend bisphosphonates as a treatment for pain relief. Denosumab is not currently licensed as a treatment for pain relief and so the committee concluded the most appropriate comparator for this appraisal is best supportive care.

7. The committee also noted a patient chart review by the manufacturer which highlighted that bisphosphonates would be prescribed or planned for future use in an estimated 50% of people with bone metastasis from other solid tumours. Zoledronic acid (80%) and disodium pamidronate (20%) are the bisphosphonates generally used in these patients. However, the committee concluded there was uncertainty about the treatments in routine use for people with bone metastases from solid tumours other than breast and prostate. It accepted that intravenous bisphosphonates namely zoledronic acid and disodium pamidronate would be used for a proportion of people, and that based on the evidence of the manufacturer it was unlikely that bisphosphonates would be used as a first-line treatment. The Committee concluded therefore that the appropriate comparators for people with bone metastases from solid tumours other than breast or prostate were best supportive care in general, and zoledronic acid or disodium pamidronate for a proportion of patients in whom they are prescribed in UK clinical practice.

8. 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 who would otherwise be prescribed zoledronic acid or disodium pamidronate, 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 cancer, denosumab was a cost-effective option as long as it was given in accordance with current NICE recommendations [7].

9. 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. Because of this, denosumab could not be considered cost-effective when compared with best supportive care and therefore could not be recommended for people with bone metastases from prostate cancer or in the general population of patients with bone metastases from solid tumours other than breast and prostate (where best supportive care was the most appropriate comparator).

10. 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.

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:

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.



[2] 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

[3] Ibandronic acid is licensed as a treatment for breast cancer patients with bone metastasis only

[4] Prostate cancer: diagnosis and treatment (NICE clinical guideline 58)

This page was last updated: 11 June 2012

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Copyright 2014 National Institute for Health and Care Excellence. All rights reserved.

Accessibility | Cymraeg | Freedom of information | Vision Impaired | Contact Us | Glossary | Data protection | Copyright | Disclaimer | Terms and conditions

Copyright 2014 National Institute for Health and Care Excellence. All rights reserved.