In its final draft guidance, the National Institute for Health and Care Excellence (NICE) does not recommend lapatinib (Tyverb, GlaxoSmithKline) or trastuzumab (Herceptin, Roche) with aromatase inhibitors for a particular type and stage of breast cancer. This is because it is unclear how much either drug can improve overall survival compared to existing treatments and they do not appear to represent value for money for the NHS.

The healthcare guidance body, NICE, is currently developing guidance for the NHS on the use of lapatinib or trastuzumab specifically as first line treatment options to delay the growth of advanced breast cancer that has spread to other parts of the body (metastatic disease), and which reacts with the hormones oestrogen or progesterone and has high levels of a protein called HER2 on the surface of its cells.Once published, the guidance will only advise on the use of these drugs alongside aromatase inhibitors (a type of hormone therapy).

This final draft document published today (Friday 27 April), is called a final appraisal determination (FAD). It follows a public consultation in February on NICE's provisional recommendations. The FAD proposes that these drugs are not recommended for use with aromatase inhibitors for this particular type and stage of breast cancer. If women are already receiving either option when the final guidance is published, then they should be able to continue treatment until they and their doctors consider it appropriate to stop.

Sir Andrew Dillon, Chief Executive of NICE said: "Having reviewed the available evidence, our committee of experts has found that while both lapatinib and trastuzumab can reduce the growth and further spread of metastatic breast cancer tumours when taken alongside the aromatase inhibitors letrozole and anastrozole, the extent to which these treatments can improve overall survival appears to be small or difficult to quantify.

"Furthermore, independent economic analyses indicate that neither treatment combination appears to be cost effective for the NHS. Confidence about the additional benefits that new treatments provide is important both for patients and for those who have responsibility for managing the resources available to the NHS.

"We have published this final draft guidance on our website so that interested parties can highlight any factual errors or appeal against the provisional recommendations. NICE guidance has not yet been issued to the NHS on the use of these drugs."

Estimates of the number of postmenopausal women diagnosed with this type and stage of breast cancer every year ranged from 50 to 2000. It is believed that most women with HER2 positive breast cancer are likely to be offered trastuzumab alongside chemotherapy as their first line option - this NICE appraisal does not look at the use of trastuzumab in this way. Lapatinib or trastuzumab would usually be considered as first line options alongside aromatase inhibitors only when chemotherapy is deemed unsuitable; however, it is unclear for how many women this would be relevant. Taking aromatase inhibitors in isolation is another existing option for these women.

Until final guidance is issued, NHS bodies should continue to make decisions locally on the funding of specific treatments.

NICE hopes to publish final guidance for the NHS in June 2012.

Ends

Notes to Editors

About the draft guidance (final appraisal determination, FAD)

1. For further information about the FAD of “Lapatinib and trastuzumab in combination with an aromatase inhibitor for the first-line treatment of metastatic hormone receptor positive breast cancer which over-expresses HER2”, visit: TA257. Please contact the NICE press office for embargoed copies of this draft guidance.

2. Neither manufacturer submitted a Patient Access Scheme (PAS). Pharmaceutical companies can consider whether they wish to reduce the acquisition cost to the NHS of a drug by proposing a PAS to the Department of Health. If agreed by the Department of Health, a PAS may enable patients to gain access to high cost drugs if the new price that the NHS is asked to pay is found to be cost effective by NICE's appraisal process.

3. The Scottish Medicines Consortium published advice for NHSScotland previously, which does not recommend lapatinib or trastuzumab taken alongside an aromatase inhibitor for women with this particular type and stage of breast cancer. For further information, visit: www.scottishmedicines.org.uk

4. Lapatinib is administered orally at a dosage of 1500mg (six tablets) per day. The acquisition cost for a lifetime of treatment of lapatinib plus the aromatase inhibitor letrozole (also taken orally) is £28,212 (£27,024 for lapatinib and £1188 for letrozole). This assumes a mean treatment-duration of 55.2 weeks and excludes administration costs.

5. NICE has not published any technology appraisal guidance on the use of lapatinib, which means that NHS decisions are made locally. Once published, this appraisal will be the first time that NICE has published guidance on the use of lapatinib.

6. Trastuzumab is administered intravenously, either with a loading dosage of 4mg/kg followed by a weekly maintenance dose of 2mg/kg, or with a loading dose of 8mg/kg followed by three-weekly maintenance doses of 6mg/kg. Based on these, the acquisition costs for a lifetime of treatment with trastuzumab plus the aromatase inhibitor anastrozole (taken orally) are £26,018 (£24,852 for trastuzumab and £1166 for anastrozole) or £26,832 (£25,666 for trastuzumab and £1166 for anastrozole) respectively. These prices assume an average patient weight of 67 kg, a mean duration of treatment of 15 months, and exclude administration, monitoring and wastage costs.

7. NICE has previously recommended trastuzumab:

• In combination with paclitaxel for women who have tumours with excessive HER2 at levels of 3+ who have not had chemotherapy for metastatic breast cancer and for whom anthracycline treatment is inappropriate - www.nice.org.uk/TA34
• For women who have early-stage HER2-positive breast cancer after they have had surgery and chemotherapy and sometimes radiotherapy - www.nice.org.uk/TA107
• For HER2-positive metastatic gastric cancer - www.nice.org.uk/TA208

8. In terms of cost effectiveness, GlaxoSmithKline estimated that the most plausible incremental cost effectiveness ratio (ICER) for lapatinib plus letrozole compared to letrozole alone is likely to be nearer £74,400 per QALY gained. Roche estimated that the most plausible ICER for trastuzumab plus anastrozole compared to anastrozole alone would be in excess of £51,000 per QALY gained. Both estimates are significantly greater than the £20,000-£30,000 range that NICE would typically deem to be a cost effective use of NHS resources. For further information about how NICE measures cost effectiveness, visit the cost effectiveness webpage.

9. The committee concluded that neither combination treatment fulfilled NICE's 'end of life' criteria. The 'end of life' criteria are supplementary pieces of advice that committees consider when appraising treatments that may extend the life of patients with a short life expectancy and that are licensed for indications that affect small numbers of people with incurable illnesses. For further information, visit the end of life treatment webpage.

10. The FAD published today (27 April) follows a second ACD which was published for public consultation in February 2012. The draft recommendations remain unchanged from the second ACD.

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.