New, draft guidance issued today (25 March) by the National Institute for Health and Clinical Excellence (NICE) does notrecommend bevacizumab (also known as Avastin and manufactured by Roche) for NHS use as an ovarian cancer treatment.
NICE is currently assessing whether bevacizumab, when used in combination with the chemotherapy treatments paclitaxel and carboplatin, would be a cost-effective treatment for women with metastatic ovarian cancer. The document issued today - which is now subject to an appeals period - supports an earlier draft of the guidance that was published in December 2012 and did notrecommend bevacizumab for this indication.
Sir Andrew Dillon, NICE Chief Executive, said:“Following a consultation period on the original draft guidance last year, the independent Appraisal Committee did not receive any additional evidence to warrant a change to the recommendations - a fact acknowledged by the manufacturer.”
Bevacizumab is licensed as a treatment for advanced ovarian cancer when used in combination with paclitaxel and carboplatin. Its licensed dose (at which it has been deemed effective and safe to use) is 15 milligrams per kilogram of body weight. However, many UK doctors use less than this (7.5mg/kg body weight) when treating patients.
The draft guidance only makes recommendations according to bevacizumab's marketing authorisation (that is, using the drug at its licensed dose)[i]. The evidence that was assessed by the Appraisal Committee indicated that the estimates obtained from the cost-effectiveness analyses were outside the range normally considered as a cost-effective use of NHS resources, leading the Committee to rule that it is not recommended for the NHS.
This draft guidance is now subject to a two-week appeals period and available to view on the NICE website. NICE has not yet published final guidance to the NHS on the use of bevacizumab (when used with paclitaxel and carboplatin) as a treatment for metastatic ovarian cancer but is expected to do so later this year. Until then, NHS bodies should make decisions locally on the funding of specific treatments.
Notes to Editors
- The draft guidance (Final Appraisal Determination or FAD) is available to viewn on the NICE website.
- Bevacizumab in combination with carboplatin and paclitaxel has a UK marketing authorisation for ‘the front-line treatment of advanced (FIGO stages IIIB, IIIC and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer'.
- The licensed dose for bevacizumab for this indication is 15 mg/kg body weight given once every three weeks in addition to carboplatin and paclitaxel for up to six cycles of treatment. This is then followed by continued use of bevacizumab as a single agent until a woman's cancer begins to progress, or for a maximum of 15 months, or until unacceptable toxicity is reached, whichever occurs earlier. However, many UK clinicians prescribe bevacizumab for this indication at an unlicensed dose of 7.5 mg/kg body weight.
- The Appraisal Committee agreed that any recommendations should be based on the licensed dose of bevacizumab because NICE is unable to make recommendations on unlicensed dosages unless specifically directed by the Department of Health. After considering the evidence, it concluded that bevacizumab plus paclitaxel and carboplatin improved progression-free survival compared with paclitaxel and carboplatin alone but that there were uncertainties over the overall survival benefit of bevacizumab with paclitaxel and carboplatin is uncertain due to patients ‘crossing over' from one arm of the study to another.
- When assessing the cost-effectiveness of the treatment, the committee noted that the manufacturer's base-case Incremental Cost Effectiveness Ratio (ICER) was roughly £144,000 per QALY gained. The Committee considered analyses from the Evidence Review Group which calculated a range of ICERs from £128,000 to £161,000 per QALY gained. The committee agreed that the range of ICERs obtained from the cost-effectiveness model of bevacizumab plus paclitaxel and carboplatin were outside the range normally considered as a cost-effective use of NHS resources.
- Bevacizumab is available in 100 mg and 400 mg vials at prices of £242.66 and £924.40 respectively (excluding VAT; 'British national formulary' [BNF] edition 63). The manufacturer estimated the cost of bevacizumab (excluding VAT and assuming there is some wastage of the drug) to be £36,078 for a patient weighing 65 kg at a dosage of 15 mg/kg every three weeks. This would amount to an average monthly cost of £2,577, although costs may vary in different settings because of negotiated discounts.
- The manufacturer of bevacizumab, Roche, has not submitted a Patient Access Scheme to the Department of Health for this appraisal. These schemes are agreed between the manufacturer and Department of Health to make the treatment in question more cost-effective for the NHS.
- Ovarian cancer is the fifth most common cancer in women in the UK[ii]. In 2009 (the date for which the most recent figures are available), there were nearly 7,000 new cases of ovarian cancer diagnosed in the UK[iii]. According to the manufacturer, the number of patients who would be eligible for this treatment has been calculated as follows:
NICE Technology Appraisal No. 55 on the use of paclitaxel in the treatment of ovarian cancer recommends the following as options for first-line treatment:
- paclitaxel in combination with a platinum-based compound or platinum-based therapy alone (cisplatin or carboplatin) as alternatives for first-line chemotherapy (usually following surgery) in the treatment of ovarian cancer.
- the choice of treatment for first-line chemotherapy for ovarian cancer should be made after discussion between the responsible clinician and the patient about the risks and benefits of the options available. In choosing between treatment with a platinum-based compound alone or paclitaxel in combination with a platinum-based compound, this discussion should cover the side-effect profiles of the alternative therapies, the stage of the woman's disease, the extent of surgical treatment of the tumour, and disease-related performance status.
- The Scottish Medicines Consortium (SMC) does not recommend the use of bevacizumab, when used within its licensed indication with paclitaxel and carboplatin for the treatment of advanced ovarian cancer.
1. The National Institute for Health and Clinical 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
- social care - the Health and Social Care Act (2012) sets out a new responsibility for NICE to develop guidance and quality standards for social care. To reflect this new role, from 1 April 2013 NICE will be called the National Institute for Health and Care Excellence (NICE) and it will become a Non-Departmental Public Body.
3. NICE produces standards for patient care:
- quality standards - these describe high-priority areas for quality improvement in a defined care or service area
- 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
- CCG Outcomes Indicator Set (formerly known as COF) - NICE develops the potential clinical health improvement indicators to ensure quality of care for patients and communities served by the clinical commissioning groups (CCGs).
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.
[i] NICE is only able to make recommendations according to a treatment's marketing authorisation. It is unable to develop recommendations on unlicensed treatments or dosage levels unless specifically instructed to do so by the Department of Health. More information is available in the Institute's process guide for technology appraisals: /proxy/?sourceUrl=http%3a%2f%2fwww.nice.org.uk%2fmedia%2fB52%2fA7%2fTAMethodsGuideUpdatedJune2008.pdf.