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NICE has issued new draft guidance not recommending the use of cetuximab (Erbitux, Merck Serono), bevacizumab (Avastin, Roche Products) and panitumumab (Vectibix, Amgen) for the treatment of metastatic colorectal cancer that has progressed after first line chemotherapy.

The draft guidance has been issued for consultation. People who are currently receiving these treatments should have the option to continue therapy until they and their clinicians consider it appropriate to stop.

Commenting on the draft recommendations Andrew Dillon, Chief Executive of NICE said: "Metastatic colorectal cancer is when the primary cancer has spread from the colon or rectum to other parts of the body, such as the liver. It can be a devastating disease for both the patient and their family. We have already recommended six treatments for various stages of colorectal cancer and are disappointed not to be able to recommend cetuximab, bevacizumab and panitumumab for this stage, but we have to be confident that the benefits justify the cost of the drugs. At present, the independent appraisal committee who drafted the recommendations does not feel it has enough clear evidence, especially in the case of bevacizumab1, to be able to recommend these drugs for use on the NHS.

"Consultees, healthcare professionals and members of the public are now able to comment on the preliminary recommendations which are available for public consultation. It is also possible for the manufacturers to provide further comment on the committee's interpretation of their products' clinical effectiveness or consider reducing the price they are asking the NHS to pay through a patient access scheme."

Comments received during this consultation will be fully considered by the Committee and following this meeting the next draft guidance will be issued.

None of these treatments have been approved for second line use of metastatic colorectal cancer in Scotland.

1 The uncertainties generated by the evidence were:

• the overall survival gain with bevacizumab plus non-oxaliplatin chemotherapy as second- or third-line treatment for people with metastatic colorectal cancer who had not responded to first-line or second-line chemotherapy.
• the estimates of overall survival for cetuximab plus irinotecan based on the mixed treatment comparison
• the magnitude of the survival benefit of panitumumab reliative to best supportive care.

Notes to Editors

About the guidance

1. The draft guidance will be available at http://guidance.nice.org.uk/TA/WaveR/102 from 5 September 2011.

2. This new appraisal is a part-review of TA118 Bevacizumab and cetuximab for the treatment of metastatic colorectal cancer http://guidance.nice.org.uk/TA118 (cetuximab part only) and of TA150.

3. NICE has previously recommended irinotecan, oxaliplatin, capecitabine, tegafur with uracil and cetuximab for the treatment of various stages of colorectal cancer.

4. None of the treatments met the criteria to be considered under NICE's special arrangements for end of life treatments. Although panitumumab currently meets the criteria, the small population criterion will not be fulfilled for much longer because the manufacturer has applied for a license extension.

5. No patient access schemes have been submitted.

6. None of these treatments have been approved for second line use of metastatic colorectal cancer in Scotland.

7. Clinical effectiveness

• Cetuximab: Cetuximab plus best supportive care prolonged life in the third-line or later setting relative to best supportive care alone
• Bevacizumab: There was no evidence to show by how long bevacizumab with non-oxaliplatin chemotherapy given as second-line treatment extended survival.
• Panitumumab: Panitumumab provided a survival benefit relative to best supportive care, but that the magnitude of this benefit was uncertain.

8. Cost effectiveness

• Cetuximab: The most plausible ICERs for cetuximab plus best supportive care were £90,000 per QALY gained and for cetuximab plus irinotecan plus best supportive care £88,000 per QALY gained, both compared with best supportive care.
• Bevacizumab: Lack of relevant evidence on clinical effectiveness meant that the assessment group were not able to carry out a cost-effectiveness evaluation of bevacizumab. The Committee also heard from Roche that it had not submitted an economic model because it did not believe it would be possible to establish that bevacizumab is cost effective as a second-line treatment for metastatic colorectal cancer.
• Panitumumab: The Committee concluded that it was not possible to specify a precise ICER for panitumumab compared with best supportive care, but that this would likely lie between £110,000 and £150,000 per QALY gained.

9. Most patients with metastatic colorectal cancer are treated with combination chemotherapy, such as oxaliplatin with fluorouracil and folinic acid.

Current guidance from NICE recommends 5-fluorouracil plus folinic acid (5-FU/FA) in combination with oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) as first line treatment options and FOLFOX or irinotecan alone as subsequent therapy in advanced colorectal cancer (technology appraisal 93). The oral analogues of 5-FU, capecitabine and tegafur, in combination with uracil (and folinic acid) are also recommended as first-line treatment options for metastatic colorectal cancer (technology appraisal 61).

Cetuximab is also recommended for people with a certain genetic profile whose metastatic disease is limited to the liver with the aim to make the metastases operable.

About NICE

10. 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

11. 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.

12. 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

13. 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.