Colorectal cancer (first line) - cetuximab: appraisal consultation document

NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE

Appraisal Consultation Document

Cetuximab for the first-line treatment of metastatic colorectal cancer

The Department of Health has asked the National Institute for Health and Clinical Excellence (NICE or the Institute) to conduct a single technology appraisal (STA) of cetuximab for the first-line treatment of metastatic colorectal cancer and provide guidance on its use to the NHS in England and Wales. The Appraisal Committee has had its first meeting to consider both the evidence submitted by the manufacturer and the views put forward by non-manufacturer consultees and commentators, and by the clinical specialist and patient expert representatives nominated for this appraisal by non-manufacturer consultees and commentators. The Committee has developed preliminary recommendations on the use of cetuximab for the first-line treatment of metastatic colorectal cancer.

This document has been prepared for consultation with the formal consultees. It summarises the evidence and views that have been considered and sets out the preliminary recommendations developed by the Committee. The Institute is now inviting comments from the formal consultees in the appraisal process (the consultees for this appraisal are listed on the NICE website, www.nice.org.uk). This document should be read in conjunction with the evidence base for this appraisal (the evaluation report) which is available from www.nice.org.uk

Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in section 1 are preliminary and may change after consultation.

The process the Institute will follow after the consultation period is summarised below. For further details, see the ‘Guide to the single technology appraisal process' (this document is available on the Institute's website, www.nice.org.uk).

The Appraisal Committee will meet again to consider the original evidence and this appraisal consultation document in the light of the views of the formal consultees.

At that meeting, the Committee will also consider comments made on the document by people who are not formal consultees in the appraisal process.

After considering feedback from the consultation process, the Committee will prepare the final appraisal determination (FAD) and submit it to the Institute.

Subject to any appeal by consultees, the FAD may be used as the basis for the Institute's guidance on the use of the appraised technology in the NHS in England and Wales.

The key dates for this appraisal are:

Closing date for comments: 15 October 2008

Second Appraisal Committee meeting: 4 November 2008

Details of membership of the Appraisal Committee are given in appendix A, and a list of the sources of evidence used in the preparation of this document is given in appendix B.

Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation.
1 Appraisal Committee's preliminary recommendations
1.1 Cetuximab is not recommended for the first-line treatment of metastatic colorectal cancer
1.2 People currently receiving cetuximab for the first-line treatment of metastatic colorectal cancer should have the option to continue treatment until they and their clinicians consider it appropriate to stop.

 

2 The technology
2.1

Cetuximab (Erbitux, Merck Serono) is a recombinant monoclonal antibody that blocks the human epidermal growth factor receptor (EGFR) and therefore inhibits the proliferation of cells that depend on EGFR activation for growth. Cetuximab is indicated for the treatment of patients with EGFR-expressing, Kirsten rat sarcoma (KRAS) wild-type metastatic colorectal cancer (mCRC):

  • in combination with chemotherapy
  • as a single agent in patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to irinotecan
2.2 One common adverse effect of cetuximab treatment is the development of skin reactions, which occur in more than 80% of patients and mainly present as an acne-like rash or, less frequently, as pruritus, dry skin, desquamation, hypertrichosis or nail disorders (for example, paronychia). The majority of skin reactions develop within the first 3 weeks of treatment. The summary of product characteristics (SPC) notes that if a patient experiences a grade 3 or 4 skin reaction, cetuximab treatment must be interrupted, with treatment being resumed only if the reaction resolves to grade 2. Other common adverse effects of cetuximab include mild or moderate infusion-related reactions such as fever, chills, nausea, vomiting, headache, dizziness or dyspnoea that occur soon after the first cetuximab infusion. For full details of adverse effects and contraindications, see the SPC.
2.3 The acquisition cost of cetuximab is £136.50 for a 5-mg/ml, 20-ml vial (excluding VAT; ‘British national formulary' [BNF] edition 56). The initial dose is 400 mg/m 2 body surface area. Subsequent weekly doses are 250 mg/m 2 each. Cetuximab treatment is recommended until there is progression of the underlying disease. Assuming vial wastage, an average person with a body surface area of 1.75 m 2 would receive seven vials per loading dose and five vials per maintenance dose, equating to a cost of £955.50 for the loading dose and £682.50 for each maintenance dose. Patients in the key clinical trials received cetuximab for approximately 8 months, equating to an average total drug acquisition cost of £22,796 per patient. Costs may vary in different settings because of negotiated procurement discounts.

 

3 The manufacturer's submission
  The Appraisal Committee (appendix A) considered evidence submitted by the manufacturer of cetuximab and a review of this submission by the Evidence Review Group (ERG; appendix B).
3.1 In the submission, the manufacturer compared a regimen of cetuximab and 5-fluorouracil (5-FU) plus folinic acid plus irinotecan (FOLFIRI) with the FOLFIRI chemotherapy regimen alone, and a regimen of cetuximab and 5-FU plus folinic acid plus oxaliplatin (FOLFOX) with the FOLFOX chemotherapy regimen alone.
3.2

The main evidence on the efficacy of cetuximab in the manufacturer's submission was derived from two randomised controlled trials (RCTs), currently not peer-reviewed.

CRYSTAL (N = 1198), a phase III, multicentre, open-label RCT, which compared cetuximab plus FOLFIRI with FOLFIRI alone, and examined progression-free survival (PFS) as the primary outcome.

OPUS (N = 337), a phase II, multicentre, open-label RCT, which compared cetuximab plus FOLFOX with FOLFOX alone, and examined response rate as the primary outcome.

  • The participants in both trials were patients with previously untreated mCRC with non-resectable metastases and an Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 at study entry. The planned treatment duration in both trials was until demonstration of progressive disease by computed tomography (CT) or magnetic resonance imaging (MRI), withdrawal of consent, and occurrence of unacceptable adverse events (AEs; CRYSTAL only) or toxicity (OPUS only).
3.3 In the submission, the manufacturer presented some data for the full analysis set (people with KRAS wild-type mCRC and KRAS mutations) for both trials. However, the main data in the submission focused on the post hoc analysis of the KRAS wild-type subgroup (n = 348 for the CRYSTAL trial; n = 134 for the OPUS trial), which was requested by the regulatory agencies and reflects the licensed indication.
3.4 The results of the full analysis set for the CRYSTAL study showed an improved PFS for cetuximab in combination with FOLFIRI compared with FOLFIRI alone (p = 0.0479) with a hazard ratio (HR) of 0.85 (95% confidence interval [CI] 0.726 to 0.998). In the OPUS study, the best overall response rate for cetuximab in combination with FOLFOX was 45.6% compared with 36.0% for FOLFOX alone. The chance for a best overall response of either complete response (CR) or partial response (PR) increased by 50% in the cetuximab plus FOLFOX group, which was not statistically significant at the 5% level (p = 0.064).
3.5 The results of the CRYSTAL trial for the KRAS wild-type subgroup showed a statistically significant increase in PFS with a median PFS of 9.9 months (95% CI 8.7 to 14.6) for cetuximab plus FOLFIRI compared with 8.7 months (95% CI 7.4 to 9.9) for FOLFIRI alone (HR = 0.684, p = 0.0167). Cetuximab plus FOLFIRI was also associated with a statistically significant increase in response rate compared with FOLFIRI alone (59.3%, 95% CI 51.6 to 66.7 versus 43.2%, 95% CI 35.8 to 50.9, p = 0.0028). The rate of potentially curative liver metastases surgery for cetuximab plus FOLFIRI was 3.5% (n = 6) compared with 2.3% (n = 4) for FOLFIRI alone (statistical significance was not reported for this outcome).
3.6 The OPUS trial results for the KRAS wild-type subgroup also showed a statistically significant increase in PFS with a median PFS of 7.7 months (95% CI 7.1 to 12.0) for cetuximab plus FOLFOX compared with 7.2 months (95% CI 5.6 to 7.4) for FOLFOX alone (HR = 0.570, p = 0.0163). Cetuximab plus FOLFOX was also associated with a statistically significant increase in response rate compared with FOLFOX alone (60.7%, 95% CI 47.3 to 72.9 versus 37.0%, 95% CI 26.0 to 49.1, p = 0.011). The rate of potentially curative liver metastases surgery for cetuximab plus FOLFOX was 11.5% (n = 7) compared with 4.1% (n = 3) for FOLFOX alone (statistical significance was not reported for this outcome).
3.7 The CRYSTAL trial also reported results for people in the KRAS wild-type subgroup who had metastatic disease confined to the liver (n = 67). There was an increase in PFS for cetuximab plus FOLFIRI compared with FOLFIRI alone, with a median PFS of 14.6 months and 9.5 months, respectively; however, this difference was not statistically significant (HR = 0.724, p = 0.437). Cetuximab plus FOLFIRI was associated with a statistically significant increase in response rate compared with FOLFIRI alone (77.1%, 95% CI 59.9 to 89.6 versus 50.0%, 95% CI 31.9 to 68.1, p = 0.0246).
3.8 Quality of life (QoL) was assessed in the CRYSTAL study using the QLQ-C30 and the EuroQol (EQ-5D) questionnaires. In the KRAS wild-type subgroup, some measures of the QLQ-C30 showed statistically significant differences between the two treatment arms in favour of the FOLFIRI-only group (mean change from baseline to worst physical functioning score, and dyspnoea scores). Thirty-seven patients completed evaluable baseline EQ-5D questionnaires; therefore, no formal statistical analyses were performed. A summary utility value was calculated for all patients, pooling all values at each visit. This provided a utility value representative of patients receiving first-line chemotherapy of 0.77 (standard deviation 0.22, n = 128). The OPUS study did not collect any QoL data.
3.9 The majority of AEs in the KRAS wild-type subgroup were in line with the existing product labelling for cetuximab or 5-FU with folinic acid plus irinotecan or oxaliplatin. In the CRYSTAL trial, the AEs that occurred more frequently in the cetuximab plus FOLFIRI group compared with the FOLFIRI-only group (a difference of 5% or more between groups) were neutropenia, constipation, dyspepsia, dyspnoea, dysgeusia, injection site reaction, erythema, hypotension, hypertrichosis and cheilitis. In the KRAS wild-type population of both the CRYSTAL and OPUS trials, the frequency of palmar-plantar erythrodysaesthesia syndrome was higher in the cetuximab plus FOLFIRI group compared with the FOLFIRI-only group (16.2% versus 2.8% [28 versus 5 patients]) and in the cetuximab plus FOLFOX group compared with the FOLFOX-only group (13.1% versus 4.1% [8 versus 3 patients]).
3.10 The manufacturer developed a semi-Markov model to simulate the disease progression and survival of a cohort of patients with EGFR-expressing, KRAS wild-type mCRC throughout first and subsequent lines of treatment (second- and third-line) including longer-term survival after successful curative surgery. The model had a cycle length of 1 week and estimated costs and benefits over a lifetime horizon (approximately 23 years).
3.11

The analysis looked at two treatment strategies: cetuximab plus FOLFIRI compared with FOLFIRI alone, and cetuximab plus FOLFOX compared with FOLFOX alone. The economic evaluation focused on a population with the following characteristics.

  • Good performance status (the majority of KRAS wild-type patients in the CRYSTAL and OPUS trials [96% and 90%, respectively] had an ECOG performance status of 0 or 1, so this was reflected in the modelled cohort)
  • Suitable for irinotecan- or oxaliplatin-containing chemotherapy
  • Metastatic disease confined to the liver, excluding people whose liver metastases were resectable at presentation
3.12 The analysis assessed the impact of cetuximab in combination with FOLFIRI or FOLFOX on the rates of potentially curative resection among people whose tumours became resectable during first-line treatment. The first-line treatment regimens were as set out in the CRYSTAL and OPUS trial protocols and administered as recorded in the trial data sets. The second-line treatment regimens of FOLFIRI or FOLFOX were taken from the published evidence, dependent on first-line treatment. If FOLFIRI was used in first line, then FOLFOX was used in the second line, and vice versa. In the third-line setting, people received best supportive care. Following successful curative surgery, people were considered tumour-free and had an increase in their estimated mean life expectancy of 4.76 years, with an observed median survival time of 3.23 years (estimated from published evidence).
3.13 Subsequent lines of treatment were modelled because both clinical trials had not generated mature overall survival data. Extrapolation techniques were used in the economic model to estimate survival benefits in the base case. These were varied in the scenario analysis.
3.14 The manufacturer considered the liver resection rates from the CRYSTAL and OPUS trials (3.5% [n = 6] for cetuximab plus FOLFIRI versus 2.3% [n = 4] for FOLFIRI alone; 11.5% [n = 7] for cetuximab plus FOLFOX versus 4.1% [n = 3] for FOLFOX alone) to be low compared with current clinical practice in the NHS. Data from a published study were therefore used to impute possible resection rates for patients with metastatic disease confined to the liver from the response rates. The correlation observed between response rates and resection rates was used to model resection rates in the base case and different scenarios in the model. The resection rates used in the base-case analysis of the CRYSTAL evaluation were 22% for cetuximab plus FOLFIRI and 12% for FOLFIRI alone, and in the OPUS evaluation were 15% for cetuximab plus FOLFOX and 7% for FOLFOX alone. Alternative values used in the scenario analyses were 55% for cetuximab plus FOLFIRI and 35% FOLFIRI alone, and 42% for cetuximab plus FOLFOX and 26% for FOLFOX alone.
3.15 The cost data were taken from the BNF edition 55 (2008) and the NHS National Tariff (2006). The cost of the KRAS test was provided by verbal communication between the manufacturer of the test and the manufacturer of cetuximab, based on ad hoc patient testing, and took into account testing of the whole patient population.
3.16 Health-related utility weights were applied to the time lived with disease at different stages of disease progression in the Markov model. Heath-related utilities were taken from clinical trials in the first- and third-line setting and estimated for the second-line setting. The utility in the period following curative surgery took into account utility in patients free of disease and patients with recurrent disease. It was assumed that patients free of disease have health-related utility equal to that of the general population. In patients with progressive disease, the utility was estimated as the weighted average of utilities in the second- and third-line setting.
3.17 The results of the base-case scenario for cetuximab plus FOLFIRI compared with FOLFIRI alone gave an incremental cost-effectiveness ratio (ICER) of £69,287 per quality-adjusted life year (QALY) gained. The results of the base-case scenario for cetuximab plus FOLFOX compared with FOLFOX alone gave an ICER of £63,245 per QALY gained.
3.18 The manufacturer presented a ‘best-case' scenario analysis which combined the most favourable resection rates (see section 3.14) and extrapolation techniques for estimating survival, and assumed no vial wastage. The best-case scenario analysis for cetuximab plus FOLFIRI compared with FOLFIRI alone gave an ICER of £34,646 per QALY gained. The results of the best-case scenario analysis for cetuximab plus FOLFOX compared with FOLFOX alone gave an ICER of £40,529 per QALY gained.
3.19 The ERG considered there to be a number of limitations with the evidence in the manufacturer's submission. It noted that the KRAS wild-type analysis was carried out post hoc and was likely to have been underpowered. It also noted that the differences in PFS of 1.2 months and 0.5 months for the CRYSTAL and OPUS trials' KRAS wild-type populations, respectively, were statistically significant in favour of cetuximab but not clinically meaningful. The ERG was also uncertain of the accuracy of the KRAS test in clinical practice. The ERG also noted that cetuximab was associated with acneiform rash.
3.20 The ERG identified a number of limitations with the manufacturer's model. It was concerned that the model focused on a much smaller patient population (people with KRAS wild-type mCRC who had metastases confined to the liver and had a high performance status) than the population defined in the appraisal scope (people with untreated mCRC) and was therefore concerned about the applicability of the results to clinical practice. The ERG was also concerned that no evidence was provided by the manufacturer to support the assumptions in the model that all patients who are suitable for treatment are identified and treated (those who are KRAS wild-type) and that patients who are not suitable for treatment (those with KRAS mutations) are not treated. Given the importance of estimating the outcomes for those treated incorrectly in reaching a conclusion on the cost effectiveness of the treatment, the ERG considered that this omission was a flaw in the model design.
3.21 The ERG was uncertain how accurate the effectiveness estimates used within the economic model were, given that they were derived from small post hoc subgroup analyses of trial results.
3.22 The ERG was not certain that all relevant costs had been included within the model, such as the cost of the necessary pretreatment with an antihistamine for people being treated with cetuximab. It also noted that the model did not take account of patients who wished to discontinue treatment as a result of the impact of AEs, and so could have overestimated the benefits gained from the addition of cetuximab. In addition, the ERG considered that the costs of the scans of the chest, abdomen and pelvis by CT or MRI, which were performed at baseline for eligibility and for a tumour assessment, should have been taken into account.
3.23 Full details of all the evidence are in the manufacturer's submission and the ERG report, which are available from www.nice.org.uk/TAxxx

 

4 Consideration of the evidence
4.1 The Appraisal Committee reviewed the data available on the clinical and cost effectiveness of cetuximab for the first-line treatment of mCRC, having considered evidence on the nature of the condition and the value placed on the benefits of cetuximab by people with mCRC, those who represent them, and clinical specialists. It was also mindful of the need to take account of the effective use of NHS resources.
4.2 The Committee noted that the licence for cetuximab limits its use to people with KRAS wild-type mCRC, a narrower indication than outlined in the scope. The Committee noted that the scope pre-dated the marketing authorisation for cetuximab, which placed this restriction on use. It heard from the clinical specialists that this indication for cetuximab reflected increasing evidence that KRAS mutation status is predictive of response to treatment and that patients whose tumours have KRAS mutations are unlikely to respond to treatment. The Committee also heard from the specialists that KRAS testing accurately identifies people with wild-type KRAS status. The test is feasible on 95% of tissue samples and is currently conducted in two centres (Leeds and Cardiff), although testing capacity is such that it may not be immediately available for all patients. In addition, commercial companies offer KRAS testing, but these are more expensive.
4.3 The Committee reviewed the clinical-effectiveness results from the two clinical trials that compared cetuximab with FOLFIRI and with FOLFOX in the KRAS wild-type subgroup. It noted the statistically significant improvements in PFS and response rates associated with cetuximab. However, it was aware that the improvement in median PFS was 1.2 months and 0.5 months in the two trials and concluded that the effectiveness of cetuximab in improving PFS was therefore limited in this population. In addition, the Committee was concerned that the KRAS subgroup analysis was based on small sample sizes and was carried out post hoc, albeit necessarily at the request of the European Medicines Agency (EMEA). However, the Committee was reassured that differential response based on KRAS status had biological plausibility given current understanding of the pathology of mCRC.
4.4 The Committee heard from the clinical specialists that cetuximab had an important potential role in downsizing secondary liver metastases to enable potentially curative surgical resection in people with KRAS wild-type mCRC. The clinical specialists reported that, of the people who show a response sufficient to enable resection of liver metastases, approximately 90% would do so within 12 weeks of treatment with cetuximab. Therefore, duration of treatment would not normally exceed 12 weeks. Patients who had no chance of a liver resection (for example, because of the distribution of hepatic metastases) or who were not fit enough for potentially curative surgery would not be treated with cetuximab, and would receive standard chemotherapy only.
4.5 The Committee considered the evidence for the effect of treatment with cetuximab on potentially curative resection of liver metastases. The results of the clinical trials showed that very small numbers of patients with KRAS wild-type mCRC went on to receive potentially curative resection (cetuximab plus FOLFIRI 3.5%, FOLFIRI alone 2.3%; cetuximab plus FOLFOX 11.5%, FOLFOX alone 4.1%) and the Committee noted that no statistical significance was reported for these differences. It heard from the clinical specialists that the number of patients receiving potentially curative metastatic surgery in the trials was lower than that seen in UK clinical practice, which is based on management by multidisciplinary teams involving highly specialised hepatic surgical services. The clinical specialists stated that a more realistic rate for potentially curative resection in current practice was approximately 12–15%, which may rise to approximately 30–35% with the addition of cetuximab. The Committee acknowledged the importance of resection rate as an endpoint in assessing the effectiveness of cetuximab. However, it was concerned that the figures put forward by the clinical specialists for resection rates of liver metastases after treatment with cetuximab were based on an analysis of data that had not yet been reported, and which it could therefore not validate. The Committee was consequently not persuaded that the accuracy of these values could be assumed. More importantly, the Committee recognised that the effectiveness of cetuximab in achieving surgical resection of liver metastases after 12 weeks of treatment had not been demonstrated.
4.6 The Committee discussed the AEs related to cetuximab. The clinical specialists advised the Committee that cetuximab is associated with an increase in an acne-like rash affecting a person's upper trunk, gastrointestinal side effects such as diarrhoea, and fatigue. The clinical specialists and patient experts explained that the acne-like rash may be predictive of response to cetuximab treatment and would not usually cause admission to hospital; therefore, it is often interpreted by people as a positive effect because it suggests that the drug is working, outweighing the burden of the rash.
4.7 Consideration was given to the results of the economic analysis submitted by the manufacturer. The Committee noted that the population modelled in the economic analysis did not fully reflect the population for which cetuximab is licensed but focused on a subgroup with a good performance status and metastatic disease confined to the liver. The Committee noted the considerable extrapolation of the trial results that was necessary to estimate survival in the economic model, and it was concerned that the extrapolation may have been unduly influenced by the larger number of data points early in the trial period. The Committee was aware that in the manufacturer's best-case scenario (see section 3.18) the incremental costs per QALY gained for cetuximab compared with FOLFIRI and FOLFOX (£35,000 and £41,000, respectively) were above the range normally considered appropriate for cost effectiveness. In addition, the Committee noted that the liver resection rates assumed in the manufacturer's best-case analyses (cetuximab plus FOLFIRI 55%, FOLFIRI alone 35%; cetuximab plus FOLFOX 42%, FOLFOX alone 26%) were higher than those reported in the clinical trials and were not considered plausible by the clinical specialists (see section 4.5). A plausible ICER for cetuximab would therefore be greater than £35,000 per QALY gained. The Committee was also aware that lower resection rates were used by the manufacturer in the base-case analysis (cetuximab plus FOLFIRI 22%, FOLFIRI alone 12%; cetuximab plus FOLFOX 15%, FOLFOX alone 7%) and this increased the incremental costs per QALY gained for cetuximab compared with FOLFIRI and FOLFOX to £69,000 and £63,000 respectively (see section 3.17). The Committee noted that evidence for a shorter duration of treatment with cetuximab (for example, 12 weeks as suggested by the clinical specialists) and its effect on resection rates had not been presented in the manufacturer's analysis.
4.8 Taking into consideration the manufacturer's cost-effectiveness estimates, the associated uncertainty in the analysis, and the limitations of the clinical evidence, including the lack of published evidence on rates of curative resection of liver metastases following treatment with cetuximab and the duration of treatment necessary to achieve curative resection, the Committee concluded that cetuximab could not be recommended as an effective use of NHS resources for the first-line treatment of mCRC.

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5 Implementation
5.1 The Healthcare Commission assesses the performance of NHS organisations in meeting core and developmental standards set by the Department of Health in ‘Standards for better health' issued in July 2004. The Secretary of State has directed that the NHS provides funding and resources for medicines and treatments that have been recommended by NICE technology appraisals normally within 3 months from the date that NICE publishes the guidance. Core standard C5 states that healthcare organisations should ensure they conform to NICE technology appraisals.
5.2 ‘Healthcare standards for Wales' was issued by the Welsh Assembly Government in May 2005 and provides a framework both for self-assessment by healthcare organisations and for external review and investigation by Healthcare Inspectorate Wales. Standard 12a requires healthcare organisations to ensure that patients and service users are provided with effective treatment and care that conforms to NICE technology appraisal guidance. The Assembly Minister for Health and Social Services issued a Direction in October 2003 that requires local health boards and NHS trusts to make funding available to enable the implementation of NICE technology appraisal guidance, normally within 3 months.
5.3

NICE has developed tools to help organisations implement this guidance (listed below). These are available on our website (www.nice.org.uk/TAXXX).

  • Slides highlighting key messages for local discussion.
  • Costing report and costing template to estimate the savings and costs associated with implementation.
  • Implementation advice on how to put the guidance into practice and national initiatives which support this locally
  • Audit support for monitoring local practice

 

6 Proposed recommendations for further research
6.1

The Committee noted the following ongoing clinical trial related to this appraisal.

  • NCT00182715 is a phase III RCT evaluating first-line use of cetuximab for mCRC (COIN trial). It aims to determine whether the addition of cetuximab to continuous oxaliplatin plus fluoropyrimidine chemotherapy improves overall survival when compared with either continuous or intermittent oxaliplatin plus fluoropyrimidine chemotherapy

 

7 Related NICE guidance
 

Published

  • Bevacizumab and cetuximab for the treatment of metastatic colorectal cancer. NICE technology appraisal guidance 118 (2007). Available from www.nice.org.uk/TA118
  • Capecitabine and oxaliplatin in the adjuvant treatment of stage III (Dukes' C) colon cancer. NICE technology appraisal guidance 100 (2006). Available from www.nice.org.uk/TA100
  • Irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer. NICE technology appraisal guidance 93 (2005) (review of TA33). Available from www.nice.org.uk/TA93
  • Improving outcomes in colorectal cancers - manual update. NICE cancer service guidance (2004). Available from www.nice.org.uk/csgcc
  • Guidance on the use of capecitabine and tegafur with uracil for metastatic colorectal cancer. NICE technology appraisal guidance 61 (2003). Available from www.nice.org.uk/TA61

Under development

NICE is developing the following guidance (details available from www.nice.org.uk):

  • Diagnosis and management of colorectal cancer. NICE clinical guideline (publication expected July 2011)

 

8 Proposed date for review of guidance
8.1 The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider whether the technology should be reviewed. This decision will be taken in the light of information gathered by the Institute, and in consultation with consultees and commentators.
8.2 It is proposed that the guidance on this technology is considered for review in December 2011. The Institute would particularly welcome comment on this proposed date.

 

David Barnett
Chair, Appraisal Committee
September 2008
Appendix A. Appraisal Committee members and NICE project team
A Appraisal Committee members

The Appraisal Committee is a standing advisory committee of the Institute. Its members are appointed for a 3-year term. A list of the Committee members who took part in the discussions for this appraisal appears below. The Appraisal Committee meets three times a month except in December, when there are no meetings. The Committee membership is split into three branches, each with a chair and vice chair. Each branch considers its own list of technologies, and ongoing topics are not moved between the branches.

Committee members are asked to declare any interests in the technology to be appraised. If it is considered there is a conflict of interest, the member is excluded from participating further in that appraisal.

The minutes of each Appraisal Committee meeting, which include the names of the members who attended and their declarations of interests, are posted on the NICE website.

Dr Ray Armstrong

Consultant Rheumatologist, Southampton General Hospital

Dr Jeff Aronson

Reader in Clinical Pharmacology, University Department of Primary Health Care, University of Oxford

Dr Darren Ashcroft

Reader in Medicines Usage and Safety, School of Pharmacy and Pharmaceutical Sciences, University of Manchester

Professor David Barnett (Chair)

Professor of Clinical Pharmacology, University of Leicester

Dr Peter Barry

Consultant in Paediatric Intensive Care, Leicester Royal Infirmary

Professor John Cairns

Public Health and Policy, London School of Hygiene and Tropical Medicine

Dr Mark Charkravarty

Director, External Relations, Procter and Gamble Health Care, Europe

Professor Jack Dowie

Health Economist, London School of Hygiene and Tropical Medicine

Ms Lynn Field

Nurse Director, Pan Birmingham Cancer Network

Dr Fergus Gleeson

Consultant Radiologist, Churchill Hospital, Oxford

Ms Sally Gooch

Independent Nursing and Healthcare Consultant

Mrs Eleanor Grey

Lay Member

Mr Sanjay Gupta

Former Service Manager in Stroke, Gastroenterology, Diabetes and Endocrinology, Basildon and Thurrock University Hospitals Foundation NHS Trust

Professor Gary McVeigh

Professor of Cardiovascular Medicine, Queen's University Belfast and Consultant Physician, Belfast City Hospital

Dr Ruairidh Milne

Senior Lecturer in Public Health, National Coordinating Centre for Health Technology, University of Southampton

Dr Neil Milner

General Medical Practitioner, Tramways Medical Centre, Sheffield

Dr Rubin Minhas

General Practitioner, CHD Clinical Lead, Medway PCT

Dr John Pounsford

Consultant Physician, Frenchay Hospital, Bristol

Dr Rosalind Ramsay

Consultant Psychiatrist, Adult Mental Health Services, Maudsley Hospital, London

Dr Stephen Saltissi

Consultant Cardiologist, Royal Liverpool University Hospital

Dr Lindsay Smith

General Practitioner, East Somerset Research Consortium

Mr Roderick Smith

Finance Director, West Kent PCT

Mr Cliff Snelling

Lay Member

Professor Ken Stein (Vice Chair)

Professor of Public Health, Peninsula College of Medicine and Dentistry, University of Exeter

Professor Andrew Stevens

Professor of Public Health, Department of Public Health and Epidemiology, University of Birmingham

Ms Nathalie Verin

Health Economics Manager, Boston Scientific UK & Ireland

Dr Colin Watts

Consultant Neurosurgeon, Addenbrookes Hospital, Cambridge

Appendix B. Sources of evidence considered by the Committee

Each technology appraisal is assigned to a team consisting of one or more health technology analysts (who act as technical leads for the appraisal), a technical adviser and a project manager.

Helen Knight

Technical Lead

Zoe Charles

Technical Adviser

Shaun Minehan

Project Manager

A

The Evidence Review Group (ERG) report for this appraisal was prepared by West Midlands Health Technology Assessment Collaboration – University of Birmingham:

  • Meads C, Round J, Tubeuf S, et al, Cetuximab for the first-line treatment of metastatic colorectal cancer, July 2008
B

The following organisations accepted the invitation to participate in this appraisal. They were invited to comment on the draft scope, the ERG report and the appraisal consultation document (ACD). Organisations listed in I were also invited to make written submissions. Organisations listed in II and III had the opportunity to give their expert views. Organisations listed in I, II and III also have the opportunity to appeal against the final appraisal determination.

I Manufacturer/sponsor:

  • Merck Serono

II Professional/specialist and patient/carer groups:

  • Association of Coloproctology of Great Britain and Ireland
  • Beating Bowel Cancer
  • Bowel Cancer UK
  • British Association of Surgical Oncology
  • Cancer Research UK
  • Macmillan Cancer Relief
  • Royal College of Nursing
  • Royal College of Pathologists
  • Royal College of Physicians, Medical Oncology Joint Special Committee
  • UK Oncology Nursing Society

III Other consultees:

  • Department of Health
  • Islington PCT
  • Nottinghamshire County PCT
  • Welsh Assembly Government

IV Commentator organisations (did not provide written evidence and without the right of appeal):

  • Department of Health, Social Services and Public Safety for Northern Ireland
  • Institute of Cancer Research
  • National Collaborating Centre for Cancer
  • NHS Quality Improvement Scotland
  • Pfizer
  • Roche Diagnostics
  • Roche Products
  • Sanofi-Aventis
C The following individuals were selected from clinical specialist and patient advocate nominations from the non-manufacturer/sponsor consultees and commentators. They gave their expert personal view on cetuximab by attending the initial Committee discussion and providing written evidence to the Committee. They are invited to comment on the ACD.
 
  • Mr Ian Beaumont, nominated by Bowel Cancer UK - patient expert
  • Dr Rob Glynne-Jones, Clinical Oncologist, Mount Vernon Hospital, nominated by Bowel Cancer UK - clinical specialist
  • Professor Timothy Maughan, Consultant Clinical Oncologist and Professor of Cancer Studies, Cardiff University, nominated by the Royal College of Physicians - clinical specialist
  • Mr Goff Norrington, nominated by Beating Bowel Cancer - patient expert
  • Mr Graeme Poston, nominated by the British Association of Surgical Oncology - clinical specialist

This page was last updated: 30 March 2010

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Accessibility | Cymraeg | Freedom of information | Vision Impaired | Contact Us | Glossary | Data protection | Copyright | Disclaimer | Terms and conditions

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