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In draft guidance issued today (9 July) by the National Institute for Health and Clinical Excellence (NICE), the drug bevacizumab (Avastin, Roche Products) is not recommended for use in combination with a taxane for patients whose breast cancer has spread to other parts of the body.

Evidence submitted to NICE by the drug manufacturer did not show bevacizumab to significantly improve or extend the lives of breast cancer patients whose tumours have spread elsewhere in the body, This uncertain clinical benefit, combined with the amount of money the NHS is being asked to pay for the drug, means NICE is unable to recommend bevacizumab (in combination with a taxane) as a first-line treatment for metastatic breast cancer).

This draft guidance has now been issued for consultation: NICE has not yet published final guidance to the NHS.

The manufacturer submitted data to the Institute’s Appraisal Committee from a clinical trial comparing bevacizumab plus paclitaxel with paclitaxel monotherapy. The study found that, on average, bevacizumab could slow the growth and spread of the tumour for five and a half months longer than paclitaxel alone. However, this did not translate into improved overall survival rates with the drug only extending patients’ lives by around an extra 7 weeks (1.7 months).

The manufacturer did not compare bevacizumab with docetaxel - a “gold standard” breast cancer treatment - despite research data being available. The Committee acknowledged the results of a clinical trial that assessed bevacizumab (used in combination with docetaxel) against doctetaxel alone. The data demonstrated that, while the research echoed the findings of the paclitaxel trial (that bevacizumab could slow the growth and spread of the cancer), the results were much less conclusive, raising questions over the true efficacy of bevacizumab.

Sir Andrew Dillon, NICE Chief Executive, said: “The clinical trial results for bevacizumab were disappointing in that they were unable to prove definitively that the drug could extend the lives of patients with metastatic breast cancer over and above currently available treatments.

“The Committee did hear evidence from a clinical expert and patient representative that the amount of time a drug can slow the growth and spread of the cancer is highly valued by patients but evidence of the length of time bevacizumab could keep the cancer under control was not robust. There was also no proof that the drug can give patients a better quality of life than paclitaxel or docetaxel.”

The Appraisal Committee also discussed the cost effectiveness of the drug (the price the NHS is being asked to pay for the level of benefit the treatment offers patients). However, when bearing in mind the uncertainties over survival rates and quality of life data, the committee concluded that the cost of bevacizumab is too high for the limited and uncertain benefit it may offer patients. The manufacturer has acknowledged that its own calculations on cost-effectiveness were ‘optimistic’.

Sir Andrew Dillon added: “It is important to remember that current breast cancer treatments like paclitaxel and docetaxel are very effective in helping to extend the lives of patients with metastatic breast cancer. For example, the study comparing bevacizumab plus paclitaxel with paclitaxel monotherapy highlighted that paclitaxel could prolong lives by just over two years, on average.”

NICE’s preliminary guidance is now available for public consultation on the NICE website until 30 July 2010. Any feedback received will be considered by the committee at their next meeting and the next version of draft guidance will be issued. Until final guidance is published, NHS bodies should make decisions locally on the funding of specific treatments.

Notes to Editors

• The guidance is available to view at http://guidance.nice.org.uk/TA/Wave21/7: (from Friday 9 July 2010).
• The appraisal consultation document (ACD) published today (9 July) states:
  • bevacizumab in combination with a taxane is not recommended for the first-line treatment of metastatic breast cancer.
• The manufacturer’s evidence was based on one trial (E2100) that compared bevacizumab plus paclitaxel with paclitaxel given on a weekly basis. The trial demonstrated that patients in the bevacizumab arm experienced around 11.3 months of progression-free survival (the amount of time bevacizumab can slow the growth and spread of the cancer) compared to 5.8 months for patients given paclitaxel. However, the trial did not produce similar results for overall survival rates, showing instead that bevacizumab plus paclitaxel only offered, on average, on extra 1.7 months of life (26.5 months compared to 24.8 months for paclitaxel monotherapy).
• Although the manufacturer did not submit any data relating to bevacizumab in combination with docetaxel, the Committee considered a recently published clinical trial (AVADO) comparing bevacizumab plus docetaxel with three-weekly docetaxel alone to be potentially relevant. The Committee noted the publicly available results from this study that demonstrated an improvement in progression-free survival of around two months for bevacizumab (at a dose of 15mg/m²) plus docetaxel, but only 0.8 months for bevacizumab (at a dose of 7.5mg/m²)plus docetaxel compared with docetaxel monotherapy.
• The committee considered the incremental cost-effectiveness ratio (ICER) of bevacizumab (the additional cost of one year of healthy life, which is expressed as the cost per quality adjusted life year, or QALY, gained). The committee concluded the best available estimate for the ICER for bevacizumab compared with docetaxel to be over £115,000 and between £117,000 and £259,000 per QALY gained when compared with paclitaxel.
• The manufacturer submitted evidence on the cost-effectiveness of bevacizumab, estimating the ICER to be around £118,000 per QALY gained. However, the manufacturer acknowledged that this calculation was ‘optimistic’.
• Bevacizumab is an angiogenesis inhibitor. It works by stopping the cancer from forming its own blood supply, stopping it growing and spreading. Tumours cannot grow any bigger than a grain of sugar without creating their own blood supply and cancer cells rely on the blood and lymphatic systems to spread around the body.
• The recommended dose of bevacizumab is 10 mg/kg of body weight given once every 2 weeks or 15 mg/kg of body weight given once every three weeks. It is given as an intravenous infusion.
• The acquisition cost of bevacizumab (excluding VAT) for a patient weighing 70 kg is approximately £1,652.38 at a dosage of 10mg/kg every 2 weeks and £2,576.78 at a dosage of 15mg/kg every three weeks. This amounts to a monthly cost of around £3,304.76 (10mg/kg given every two weeks) and £3,435.70 (15mg/kg given every three weeks).
• The total average cost per patient of bevacizumab plus paclitaxel is estimated to be £33,649 compared to paclitaxel alone, which costs around £7,720 per patient (costs are taken from the British National Formulary, edition 58).

About NICE

1. The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance 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 and procedures within the NHS
• clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.