The clinical and cost effectiveness of two breast cancer drugs that may be offered alongside hormone therapy to some postmenopausal women who have a particular type of the disease has not been clearly demonstrated. Draft guidance from the National Institute for Health and Clinical Excellence (NICE) therefore recommends against their use in the NHS for this condition.

The draft guidance looks at the use of lapatinib (also called Tyverb, manufactured by GlaxoSmithKline) or trastuzumab (Herceptin, Roche) as a first-line treatment for a specific type of advanced breast cancer that has spread to other parts of the body (metastatic) The appraisal only looks at their use alongside a type of hormone therapy called an aromatase inhibitor. This combination is used when the breast cancer cells have receptors for the hormone oestrogen and also high levels of a protein called HER2 or erbB2.

Postmenopausal women who choose not to have chemotherapy, or for whom it is not a suitable option, are most likely to be offered aromatase inhibitors, either by themselves, or in combination with one of these drugs.

Following a public consultation on its initial findings last December, NICE's latest draft guidance (the final appraisal determination) is still unable to recommend the use of either drug with aromatase inhibitors as NHS treatment options. However, women already receiving either of the drugs with aromatase inhibitors should be able to continue to do so until they and their doctors consider it appropriate to stop.

Sir Andrew Dillon, Chief Executive of NICE, said: "Doctors treating women with metastatic breast cancer hope to relieve their symptoms, prolong survival and maintain a good quality of life with minimal side effects. Unfortunately the manufacturers of lapatinib and trastuzumab didn't give our independent committee convincing evidence to show how much using either drug with an aromatase inhibitor could benefit these women, more than using the aromatase inhibitors by themselves. The cost effectiveness of the drugs was also significantly uncertain.

"NICE's job is to ensure patients have access to the best treatments possible within the NHS's limited resources. We have published the latest version of our draft guidance on our website so that interested parties can highlight any factual errors or appeal against our provisional recommendations."

The draft guidance specifically looks at "metastatic hormone-receptor-positive breast cancer that over-expresses human epidermal growth factor receptor 2 (HER2)". Alternative first-line treatments for women with this type of cancer could include aromatase inhibitor monotherapy, or chemotherapy.

Registered stakeholders wishing to appeal NICE's draft recommendations have until 15 July 2011 to do so. If no appeals are received, NICE expects to publish its final guidance for the NHS on 24 August 2011.

Until NICE issues final guidance, decisions on the funding of specific treatments should be made locally by NHS bodies.

Notes

About the draft guidance

1. For further information about the final appraisal determination of "lapatinib or trastuzumab in combination with an aromatase inhibitor for the first-line treatment of metastatic hormone-receptor-positive breast cancer that overexpresses HER2", visit: here. Contact the press office for embargoed copies of the draft guidance.

2. NICE has previously recommended trastuzumab for:

- Advanced or metastatic breast cancer
- HER2-positive metastatic gastric cancer
- Early-stage HER2-positive breast cancer

While there is no legal obligation for NHS organisations to comply with NICE guidance that does not recommend particular medicines, it is considered best practice for them to do so.

3. Breast cancer that has spread to other parts of the body is known as metastatic breast cancer. For some women, the hormones oestrogen or progesterone stimulate breast cancer cells to grow. This type of breast cancer is known as hormone-receptor positive (HR+). Human epidermal growth factor receptor 2-positive (HER2-positive) means that there are high levels of a protein called HER2 on the surface of the cancer cells. Another protein produced naturally in the body attaches itself to the HER2 protein, which makes the cancer grow.

4. Lapatinib plus an aromatase inhibitor (letrozole): The acquisition cost for a lifetime of treatment with lapatinib plus letrozole is £28,524 (£27,336 for lapatinib and £1,188 for letrozole) per patient. This price assumes a mean duration of treatment of just over 55 weeks and excludes administration costs.

5. The Committee concluded that the additional benefit provided by lapatinib was small and uncertain and that the incremental cost effectiveness ratio (ICER) for lapatinib plus letrozole compared with letrozole alone was likely to be in excess of £74,400 per QALY gained as estimated by the manufacturer. No robust evidence had been presented to indicate that lapatinib plus an aromatase inhibitor compared with an aromatase inhibitor alone offered a 3-month survival gain. The Committee concluded that treatment with lapatinib plus an aromatase inhibitor did not fulfil NICE's 'end of life' criteria.

6. Trastuzumab plus an aromatase inhibitor (anastrozole): The acquisition cost for a lifetime of weekly treatment with trastuzumab plus anastrozole is £26,018 (£24,852 for trastuzumab and £1166 for anastrozole). This price assumes an average patient weight of 67 kg, a mean duration of treatment of 15 months, and excludes administration, monitoring and wastage costs. If trastuzumab plus anastrozole was given once every three weeks, the cost would be approximately £26,832 (£25,666 for trastuzumab and £1166 for anastrozole) assuming an average patient weight of 67 kg, a mean treatment period of 15 months and excluding administration, monitoring and wastage costs.

7. The Committee concluded that the additional benefit provided by trastuzumab was uncertain. The ICER for trastuzumab plus anastrozole compared with anastrozole alone would be in excess of £51,000 which had been estimated by the manufacturer. The Committee also concluded that there was uncertainty about the total size of the population for whom trastuzumab might be used and that it is likely to be larger than 7100 patients as stated by the manufacturer. The Committee concluded that treatment with trastuzumab plus an aromatase inhibitor did not fulfil NICE's 'end of life' criteria.

Source:
NICE