NICE draft guidance does not recommend bevacizumab as advanced ovarian cancer treatment
The National Institute for Health and Care Excellence (NICE) has published draft guidance today (18 December) on the use of bevacizumab (Avastin, Roche) as a treatment for women with advanced ovarian cancer. The draft guidance does not recommend the use of bevacizumab when used with paclitaxel and carboplatin for people with advanced disease, as a cost-effective treatment for the NHS.
This draft guidance has now been issued for consultation: NICE has not yet published final guidance to the NHS.
The Institute is aware that UK clinical practice is to prescribe bevacizumab at a dosage below that for which it is currently licensed[i].
The evidence submitted by the manufacturer involved clinical trials using both the licensed and the commonly used (lower) unlicensed dose. The medicines regulator looked at both but only issued a licence for the higher dose. The clinical trial which assessed the licensed dose of bevacizumab (GOG-0218) was therefore used by NICE's independent advisory committee, although it noted there were inconsistencies in how results were recorded and questioned whether the trial's ‘censored' or ‘uncensored' data would be the most appropriate to appraise[ii].
Sir Andrew Dillon, NICE Chief Executive, said:“Although it was acknowledged that bevacizumab, when used in combination with paclitaxel and carboplatin, appears to provides benefit to some patients by delaying the spread of their cancer, it was unclear whether this translated into an overall survival benefit. There was no evidence to show that the clinical benefit of the treatment justifies its cost, when compared to existing treatments - an important factor to consider, especially as the NHS has finite resources.”
When assessing the treatment's cost-effectiveness, the Appraisal Committee noted that all evidence, including that which was submitted by the manufacturer, suggested the Incremental Cost Effectiveness Ratio (ICER) was likely to be between £128,000 and £161,000 per QALY gained. As a result, the committee concluded it could not recommend bevacizumab as a cost-effective use of limited NHS resources.
NICE's preliminary guidance is now available for public consultation until 22 January 2013. Comments can be made via the NICE website. Any feedback received during this consultation will be considered by the committee and, following this meeting, the next version of draft guidance will be issued.
Final guidance on the use of bevacizumab (when used with paclitaxel and carboplatin) as a treatment for metastatic ovarian cancer is expected to be published next year. Until then, NHS bodies should make decisions locally on the funding of specific treatments.
Notes to Editors
- The guidance is available to view from Tuesday 18 December 2012.
- 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 manufacturer submitted data from two clinical trials as evidence of bevacizumab's effectiveness for this indication. One (the GOG-0218 trial) assessed bevacizumab at its licensed dose while the other (the ICON7 trial) assessed its effectiveness at the unlicensed dose.
- The Appraisal Committee concluded that the two clinical trials were difficult to compare because of factors including different patient selection criteria, bevacizumab dose and duration of treatment, and definitions of progression.
- The committee accepted the results of the GOG-0218 trial as being the most relevant to the first-line treatment of patients with advanced ovarian cancer. However, there were concerns from the independent Evidence Review Group about inconsistent reporting of progression-free survival data. There was also uncertainty about whether the data's ‘censored' or ‘uncensored' results for progression-free survival would be most relevant to UK clinical practice. The committee also noted 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.
- The Appraisal Committee concluded that the censored results of the GOG-0218 trial were most relevant to UK clinical practice, although the committee acknowledged the possibility that the censoring introduced a bias. It noted that, when taking these censored results into consideration, the median progression-free survival benefit (the time point in the trial at which the 50% of people's cancers began to progress once again) associated with bevacizumab plus paclitaxel and carboplatin was six months more than paclitaxel and carboplatin alone. All analyses of progression-free survival data submitted by the manufacturer to the Appraisal Committee (both censored and uncensored data), showed a difference in median progression-free survival benefit of between 3.8 and 6 months. Therefore, the committee concluded that bevacizumab plus paclitaxel and carboplatin improved progression-free survival compared with paclitaxel and carboplatin alone.
- 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[iii]. 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[iv]. 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 Care 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.
[i] Bevacizumab (in combination with paclitaxel and carboplatin) is licensed for people with metastatic ovarian cancer at a dose of 15mg per kg of body weight. However, many UK clinicians prescribe bevacizumab for this indication at an unlicensed dose of 7.5mg/kg body weight.
[ii] The trial's ‘uncensored' and ‘censored' results relate to a blood test given to patients to check levels of CA125 in their bloodstream. Raised levels can indicate ovarian cancer or, if someone already has the disease, a rise in their CA125 levels could indicate that the disease is progressing (although it can take up to six months for this to become apparent). The ‘uncensored' data from the GOG-0218 trial recorded any rise in CA125 levels as evidence that a patient's cancer had progressed. In comparison, the ‘censored' data removed any results indicating a rise in CA125 levels from further analysis. The Appraisal Committee heard that roughly one third of patients with ovarian cancer do not express CA125 and it is not used in UK clinical practice as the sole marker to indicate disease progression. Therefore, the committee concluded that the GOG-0218 trial's censored data for progression-free survival was most relevant to UK clinical practice, although acknowledged the possibility that censoring data introduced a bias.
This page was last updated: 17 December 2012