NICE seeks views on two breast cancer drugs

The National Institute for Health and Care Excellence (NICE) has published draft guidance today (Tuesday 14 February), which proposes to advise the NHS that lapatinib or trastuzumab with aromatase inhibitors should not be prescribed for a particular type and stage of breast cancer. This is because the extent to which they can improve overall survival compared to existing treatments is uncertain and so they do not appear to represent value for money for the NHS.

The healthcare guidance body, NICE is currently developing guidance for the NHS whether or not it should offer lapatinib (Tyverb, GlaxoSmithKline) or trastuzumab (Herceptin, Roche) specifically as first line treatment options to delay the growth of advanced breast cancer that has already spread to other parts of the body, and whose tumour cells both react with the hormones oestrogen or progesterone and have high levels of a protein called HER2 on their surface. The guidance will only advise on the use of these drugs alongside aromatase inhibitors (a type of hormone therapy).

This second consultation draft comes after Roche's appeal against some of the committee's initial findings was upheld, and the committee subsequently discussed the points again at a further meeting in January 2012.

Experts estimate that between 50 and 2,000 postmenopausal women are diagnosed with this type and stage of breast cancer every year. It is believed that most of these women are likely to be offered trastuzumab alongside chemotherapy as their first line option. Lapatinib or trastuzumab would usually be considered as first line options alongside aromatase inhibitors only when chemotherapy is deemed unsuitable; however, it is unclear how many women this would be relevant to. Taking aromatase inhibitors in isolation is another existing first line option for these women.

The draft guidance (called an appraisal consultation document) has been published for consultation; it has not been issued to the NHS. It 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 that these treatments can improve overall survival appears to be small or undefined.

"Furthermore, independent economic analyses indicate that both treatment combinations do not appear to be cost effective for the NHS because they have uncertain clinical benefits for the price that the NHS is being asked to pay. Confidence about the additional benefits new treatments bring is important both for patients and for those who have responsibility for managing the resources available to the NHS.

"We have published this draft guidance on our website as an opportunity for stakeholders and the public to contribute to its development."

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

The deadline for comments received is 5pm on Tuesday 6 March. The committee will then meet again to review all submissions.


Notes to Editors

About the draft guidance (appraisal consultation document, ACD)

1. For further information about the ACD 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:

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 NHS Scotland 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:

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 -
  • For women who have early-stage HER2-positive breast cancer after they have had surgery and chemotherapy and sometimes radiotherapy -
  • For HER2-positive metastatic gastric cancer -

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 higher than £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 bracket that NICE would typically deem to be a cost effective use of NHS resources. Note that the totals generated are not prices that the NHS would actually pay, but rather monetary values that can be used to compare the cost effectiveness of medicines. For further information about how NICE measures cost effectiveness, visit:

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:

10. The ACD follows an earlier draft (called the final appraisal determination, FAD) from July 2011, which went back to the committee for further discussion after Roche submitted an appeal. This appeal was upheld by an independent panel in November 2011. In the FAD, the committee had concluded that trastuzumab did not fulfil the small population criterion within NICE's “end of life criteria”. Roche appealed this decision because when NICE appraised trastuzumab for HER2-positive metastatic gastric cancer in 2010 (TA208), the committee responsible for developing this guidance concluded that the number of patients who are diagnosed annually with the conditions for which trastuzumab is indicated (an estimated 7,158 people in total) did fulfil this criterion. Therefore, for consistency the committee revised their decision following the appeal, and so the new ACD states that trastuzumab plus an aromatase inhibitor does fulfil the small patient population criterion. However, as trastuzumab still does not fulfil the criterion for short life expectancy (normally less than 24 months), the committee is still not able to provisionally advise that special consideration under the end of life criteria should be given. For further information about the appeal, visit:

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.

This page was last updated: 13 February 2012

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