Head and neck cancer - cetuximab

Transcription

1 Documentation U N H P C Head and neck cancer - cetuximab Cetuximab for the treatment of head and neck cancer Guidance type: Technology appraisal Date issued: juin 2008 We will consult on our review plans for this guidance in mars Reference: TA145 Summary Cetuximab in combination with radiotherapy is recommended as a possible treatment for people with locally advanced squamous cell cancer of the head and neck if: * they have a Karnofsky performance-status score of 90% or more, and * all forms of platinum-based chemotherapy are considered inappropriate Healthcare professionals should not stop prescribing cetuximab in combination with radiotherapy for people who were already receiving it when the guidance was issued, but who do not fulfil the above criteria. These patients should be able to carry on taking cetuximab until they and their healthcare professionals decide that it is the right time to stop treatment. When assessing Karnofsky performance-status score, healthcare professionals should take into account any disabilities that might affect a person's ability to carry out daily activities. Documents For healthcare professionals * TA145 Head and neck cancer - cetuximab: guidance * TA145 Head and neck cancer - cetuximab: quick reference guide For patients, carers and the public * TA145 Head and neck cancer - cetuximab: understanding NICE guidance Background information * NICE issues guidance on the use of cetuximab for the treatment of head and neck cancer Implementing this guidance Any further information NICE has produced to help the NHS implement this guideline locally is linked to below: * TA145 Head and neck cancer - cetuximab: costing template * TA145 Head and neck cancer - cetuximab: audit support Union Nationale Hospitalière Privée de Cancérologie Documentation à l'usage des adhérents

2 Issue date: June 2008 Review date: March 2011 Cetuximab for the treatment of locally advanced squamous cell cancer of the head and neck This guidance was developed using the single technology appraisal process NICE technology appraisal guidance 145

3 NICE technology appraisal guidance 145 Cetuximab for the treatment of locally advanced squamous cell cancer of the head and neck Ordering information You can download the following documents from The full guidance (this document). A quick reference guide for healthcare professionals. Information for people with locally advanced squamous cell cancer of the head and neck and their carers ( Understanding NICE guidance ). Details of all the evidence that was looked at and other background information. For printed copies of the quick reference guide or Understanding NICE guidance, phone NICE publications on or publications@nice.org.uk and quote: N1608 (quick reference guide) N1609 ( Understanding NICE guidance ). This guidance is written in the following context This guidance represents the view of the Institute, which was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. The guidance does not, however, override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. National Institute for Health and Clinical Excellence MidCity Place 71 High Holborn London WC1V 6NA National Institute for Health and Clinical Excellence, All rights reserved. This material may be freely reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the express written permission of the Institute.

4 Contents 1 Guidance 4 2 The technology 4 3 The manufacturer s submission 5 4 Consideration of the evidence 11 5 Implementation 15 6 Recommendations for further research 17 7 Related NICE guidance 17 8 Review of guidance 17 Appendix A: Appraisal Committee members and NICE project team 18 Appendix B: Sources of evidence considered by the Committee 22

5 This guidance was developed using the single technology appraisal (STA) process 1 Guidance 1.1 Cetuximab in combination with radiotherapy is recommended as a treatment option only for patients with locally advanced squamous cell cancer of the head and neck whose Karnofsky performancestatus score is 90% or greater and for whom all forms of platinumbased chemoradiotherapy treatment are contraindicated. 1.2 Patients currently receiving cetuximab in combination with radiotherapy for the treatment of locally advanced squamous cell cancer of the head and neck who do not meet the criteria outlined in section 1.1 should have the option to continue therapy until they and their clinicians consider it appropriate to stop. 1.3 When using Karnofsky performance-status score, clinicians should be mindful of the need to secure equality of access to treatment for patients with disabilities. Clinicians should bear in mind that people with disabilities may have difficulties with activities of daily living that are unrelated to their prognosis with respect to cancer of the head and neck. In such cases clinicians should make appropriate judgements of performance status taking into account the person's usual functional capacity and requirement for assistance with activities of daily living. 2 The technology 2.1 Cetuximab (Erbitux, Merck Pharmaceuticals) is a chimeric immunoglobulin G monoclonal antibody that competes for epidermal growth factor receptor (EGFR) binding sites on the external surface of the cell membrane. Binding of cetuximab to EGFR prevents activation of tyrosine kinase within cells, eventually resulting in apoptosis. Cetuximab, in combination with radiotherapy, NICE technology appraisal guidance 145 4

6 is licensed for the treatment of patients with locally advanced squamous cell cancer of the head and neck. For further information, see the summary of product characteristics (SPC). 2.2 The most common side effects of cetuximab are mild or moderate infusion-related reactions such as fever, chills, nausea, vomiting, headache, dizziness or dyspnoea that occur soon after the first cetuximab infusion. Skin reactions develop 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 therapy. For full details of side effects and contraindications, see the SPC. 2.3 The acquisition cost of cetuximab is for a 5-mg/ml, 20-ml vial (excluding VAT; British national formulary, edition 55). The initial dose is 400 mg/m 2 body surface area. Subsequent weekly doses are 250 mg/m 2 each. A course of treatment can range from 2 to 8 weeks. Assuming a body surface area range of 1.6 m 2 to 1.8 m 2, the drug cost of a course of treatment comprising two to eight cycles is 4778 to 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). The Committee further considered evidence submitted by consultees and commentators requested by the Institute after the appeal. 3.1 The manufacturer s submission approached the decision problem by comparing cetuximab plus radiotherapy with radiotherapy alone. The manufacturer specified that the population under consideration consisted of people with locally advanced squamous cell cancer of NICE technology appraisal guidance 145 5

7 the head and neck for whom chemotherapy is considered inappropriate but for whom radiotherapy is suitable. The outcome measures specified in the decision problem were duration of locoregional control, overall survival, progression-free survival and safety. 3.2 The manufacturer s submission presented evidence on the clinical effectiveness of cetuximab plus radiotherapy based on a single randomised controlled trial (RCT; the Bonner trial) that compared cetuximab plus radiotherapy with radiotherapy alone in people with stage III or IV non-metastatic squamous cell cancer of the oropharynx, hypopharynx or larynx. Criteria for eligibility included medical suitability for definitive radiotherapy, a Karnofsky performance-status score of at least 60%, and normal haematopoietic, hepatic and renal function. Patients were not included in the trial if they had undergone surgery or had previously received radiotherapy for head and neck cancer. The primary outcome measure was the duration of control of locoregional disease. The secondary endpoints were overall survival, progression-free survival, response rate and safety. 3.3 Final analyses of the trial showed that the 211 people in the cetuximab plus radiotherapy arm had a longer median duration of locoregional control than the 213 people in the radiotherapy-alone arm (24.4 versus 14.9 months, p = 0.005, hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.52 to 0.89) and greater median overall survival (49.0 versus 29.3 months, p = 0.03, HR 0.74, 95% CI 0.57 to 0.97). 3.4 The manufacturer s submission presented a de novo economic analysis that compared cetuximab plus radiotherapy with radiotherapy alone. The model used individual patient data from the RCT to estimate costs and health effects during the trial period for each patient. When trial observations were censored, the model extrapolated costs and health effects. NICE technology appraisal guidance 145 6

8 3.5 The base-case analysis compared cetuximab plus radiotherapy with radiotherapy alone and resulted in an incremental costeffectiveness ratio (ICER) of 6400 per quality-adjusted life year (QALY) gained. The manufacturer undertook a univariate sensitivity analysis, which demonstrated that the model was not sensitive to change when assessing the effect of uncertainty in a variety of inputs. Relatively large variability was observed when the timeframe of the analysis changed from a lifetime to the period of the trial follow-up, resulting in an ICER of 20,000 per QALY gained. 3.6 The ERG reviewed the evidence on clinical and cost effectiveness submitted by the manufacturer. The ERG judged that the one trial included in the manufacturer s submission was well conducted and that the results for the primary endpoints appeared robust. However, the ERG noted that the majority of patients in the trial population had a good performance status (Karnofsky performance-status score ranged from 60% to 100% but was most commonly 90%), and chemotherapy would be expected to be suitable for them. Therefore, the population of the trial did not match the population described in the decision problem, that is, patients for whom chemoradiotherapy is considered inappropriate. Furthermore, there are differences between the radiotherapy regimens used in the trial and those most commonly used in UK clinical practice. 3.7 The ERG reviewed the economic model and identified a number of concerns. The most important of these was that the only RCT informing the economic analysis (the Bonner trial) did not match the patient population specified in the manufacturer s decision problem. The manufacturer provided a set of possible criteria for defining patients for whom chemoradiotherapy is inappropriate, based on discussions with a small number of oncologists. In addition, the manufacturer was asked to provide information on the number of NICE technology appraisal guidance 145 7

9 patients in the trial for whom chemoradiotherapy was considered inappropriate. However, the manufacturer stated that it was unable to provide analyses based on these criteria as the RCT was not designed or statistically powered to assess subgroups of patients for whom chemoradiotherapy may be considered inappropriate. 3.8 In addition, the ERG identified a series of issues and uncertainties about the methods for extrapolation of the trial data, assessment of health-related quality of life (HRQoL), and estimation of resource use and costs. The ERG concluded that the methods used were probably appropriate but was unable to determine, in the majority of cases, the likely influence of using alternative methods on the results of the economic model. However, the ERG concluded that altering the method of extrapolation would be unlikely to cause the ICER to increase to above 20, The ERG undertook additional work to examine the robustness of the base-case results to the assumptions made in the manufacturer s cost-effectiveness model about HRQoL, resource use and cost. The ERG concluded that any inaccuracies would have to be very large to have a material effect on the conclusions of the manufacturer s cost-effectiveness analysis The ERG felt that although the economic analyses undertaken by the manufacturer demonstrated that cetuximab in combination with radiotherapy was cost effective compared with radiotherapy alone under a broad range of different assumptions (assuming a threshold of 20,000 per QALY), the cost-effectiveness estimates might not be directly applicable to the population specified in the manufacturer s decision problem (that is, patients for whom chemoradiotherapy is considered inappropriate). This was because the clinical study on which the economic analysis was based included a substantial proportion of patients for whom chemoradiotherapy would be considered suitable. NICE technology appraisal guidance 145 8

10 3.11 Following an appeal hearing, the Appeal Panel requested that the manufacturer provide subgroup survival data (derived from the Bonner trial) for each of the separate Karnofsky performance-status score subgroups (Karnofsky performance-status scores of 100%, 90%, 80%, 70% and less than 70%). The manufacturer stated that the number of patients in some of the subgroups was small (numbers ranged from 12 to 91), and this should be taken into consideration when interpreting these data. For patients with Karnofsky performance-status scores of 100% and 90%, the survival HRs were in favour of cetuximab plus radiotherapy over radiotherapy alone (HR 0.61, 95% CI 0.28 to 1.31, and HR 0.58, 95% CI 0.39 to 0.88 for Karnofsky performance-status scores of 100% and 90%, respectively). For patients with Karnofsky performance-status scores of 80%, 70% and less than 70%, the survival HRs were in favour of radiotherapy alone over cetuximab plus radiotherapy (HR 1.11, 95% CI 0.69 to 1.77; HR 1.22, 95% CI 0.53 to 2.78; and HR 3.41, 95% CI 0.65 to 17.7, respectively) The manufacturer was further asked by the Appeal Panel to provide cost-effectiveness estimates for the subgroup analyses described in section The analyses were conducted using the manufacturer s original cost-effectiveness model. The manufacturer s analysis gave ICERs for cetuximab in combination with radiotherapy versus radiotherapy alone of 13,151 and 4,467 per additional QALY gained for patients with Karnofsky performance-status scores of 100% and 90%, respectively. For patients with Karnofsky performance-status scores of 70%, radiotherapy alone dominated cetuximab in combination with radiotherapy (that is, radiotherapy alone was more effective in terms of QALYs gained and was less expensive). For patients with Karnofsky performance-status scores of 80% and less than 70%, the manufacturer reported ICERs for cetuximab in combination with NICE technology appraisal guidance 145 9

11 radiotherapy versus radiotherapy alone of 58,200 and 37,000 per additional QALY gained, respectively Following the appeal hearing, the Institute invited the manufacturer and consultees and commentators to provide or highlight further evidence on the efficacy of carboplatin monotherapy in combination with radiotherapy, and on the safety or toxicity of carboplatin with fluorouracil and radiotherapy in patients with locally advanced squamous cell cancer of the head and neck. The manufacturer undertook a literature review and identified 22 studies on the efficacy of carboplatin monotherapy and radiotherapy, none of which were phase III studies or meta-analyses. Six of the 22 studies reported median overall survival estimates, which ranged from 6.7 months to 30 months. The manufacturer considered the median overall survival estimate of 30 months reported by Jeremic and colleagues (n = 53) to be the most robust. The manufacturer further identified nine published studies on the efficacy and safety of carboplatin with fluorouracil and radiotherapy, of which three were phase III trials. The phase III studies reported median overall survival estimates of 23 months, 20 months and 19 months (n = 113, 109 and 64, respectively), and haematological toxicities (grade 3 or 4 acute toxicities) of 23% and 29.5% (n = 113 and 64, respectively). Consultees highlighted that there was little published evidence on the efficacy of carboplatin-based chemoradiotherapy compared with cisplatin-based chemoradiotherapy or with radiotherapy alone, but that carboplatinbased chemoradiotherapy can be used as a treatment for patients for whom cisplatin-based chemoradiotherapy is not an option Full details of all the evidence are in the manufacturer s submission and the ERG report, which are available from NICE technology appraisal guidance

12 4 Consideration of the evidence 4.1 The Appraisal Committee reviewed the data available on the clinical and cost effectiveness of cetuximab, having considered evidence on the nature of the condition and the value placed on the benefits of cetuximab by people with locally advanced squamous cell cancer of the head and neck, 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 considered that the decision problem described in the manufacturer s submission was reasonable, but noted that the population specified excluded people for whom chemotherapy is suitable. Therefore the decision problem did not reflect the entire population of people with locally advanced squamous cell cancer of the head and neck for whom cetuximab might be considered as a treatment option according to its licensed indication. 4.3 The Committee considered current UK clinical practice in the treatment of locally advanced squamous cell cancer of the head and neck. It heard from the clinical specialist who attended the meeting that chemoradiotherapy is the standard care for patients with stage lll and IV squamous cell cancer of the head and neck. However, there are patients for whom chemoradiotherapy is considered inappropriate (for example, patients with co-existing medical conditions and poor performance status). Chemoradiotherapy carries a high risk of adverse effects and patients should be willing and fit enough to be treated. The clinical specialist and patient experts were of the opinion that for patients whose condition required an alternative to chemoradiotherapy, cetuximab plus radiotherapy was a useful option because of its relatively low toxicity profile compared with chemotherapy. 4.4 The Committee heard from the clinical specialist that there is considerable variation in clinical practice across the UK. There are NICE technology appraisal guidance

13 4.5 The Committee considered the evidence on the clinical effectiveness of cetuximab in combination with radiotherapy for the treatment of locally advanced squamous cell cancer of the head and neck. It noted that there was only one relevant RCT that compared cetuximab plus radiotherapy with radiotherapy alone in people with non-resected disease (the Bonner trial). The Committee noted that the trial had started at a time when radiotherapy rather than chemoradiotherapy was the standard treatment. The Committee accepted that cetuximab with radiotherapy had been shown to be more effective than radiotherapy alone in the population represented in the trial. 4.6 The Committee noted that there were no trials that compared cetuximab plus radiotherapy directly with any platinum-based chemoradiotherapy. The Committee understood that chemoradiotherapy is considered to be standard treatment for patients unless there are reasons to contraindicate its use, and that cetuximab plus radiotherapy might have advantages over chemoradiotherapy in terms of reduced toxicity. However, the Committee was not presented with any evidence comparing cetuximab plus radiotherapy with chemoradiotherapy on which an estimate of the clinical and cost effectiveness of cetuximab in combination with radiotherapy could be based. Therefore the Committee was unable to make any recommendations on its use as an alternative to chemoradiotherapy. NICE technology appraisal guidance

14 4.7 The Committee considered the use of cetuximab in combination with radiotherapy in the population specified in the manufacturer s decision problem, that is, the subgroup of patients for whom chemoradiotherapy was considered to be unsuitable by the manufacturer. The Committee noted that the population in the relevant RCT was relatively fit: more than two thirds had a Karnofsky performance-status score of 90% or above and all had normal haematopoietic, hepatic and renal function. The manufacturer was unable to provide information on the number of patients in the RCT for whom chemoradiotherapy would have been inappropriate, or on the effectiveness of cetuximab plus radiotherapy in this subgroup. 4.8 The Committee considered that patients with lower Karnofsky performance-status scores would form most, if not all, of the population for whom chemoradiotherapy would be considered inappropriate in clinical practice. The Committee discussed the subgroup analyses of the median overall survival data according to Karnofsky performance-status scores provided by the manufacturer and reported in the European public assessment report published by the European Medicines Agency. Although recognising the difficulties in interpreting the subgroup analyses, the Committee noted that no clinical benefit had been demonstrated for cetuximab in combination with radiotherapy in patients with a Karnofsky performance-status score of 80% or less. The Committee concluded that given the absence of clinical benefit (albeit with wide confidence intervals) it could not make the subgroup of patients with Karnofsky performance-status scores of 80% or less the basis for a positive recommendation to use cetuximab in combination with radiotherapy. Indeed, the Committee noted that the European public assessment report stated that the overall impression of all subgroup analyses is that the add-on effect of cetuximab tends to be small or absent irrespective of outcome NICE technology appraisal guidance

15 measure in patients with poor prognosis (estimated from median overall survival). 4.9 The Committee then considered patients with a Karnofsky performance-status score of 90% or greater and explored situations in which chemoradiotherapy might be unsuitable for them. The Committee reviewed the criteria proposed by consultees for identifying patients with good performance status and for whom cisplatin-based chemoradiotherapy would be inappropriate. It noted from consultees that some patients who are unable to tolerate the nephrotoxicity, ototoxicity and fluid overload from cisplatin-based chemoradiotherapy prefer carboplatin-based chemoradiotherapy. The Committee was made aware by consultees that although carboplatin does not have a UK marketing authorisation for the treatment of locally advanced squamous cell cancer of the head and neck, carboplatin-based combination regimens have been studied in this condition and are sometimes used to treat this condition in UK clinical practice. However, the Committee also heard that carboplatin-based regimens are associated with haematological adverse effects, particularly myelosuppression. The Committee concluded that although carboplatin-based chemoradiotherapy is a treatment option for some patients for whom cisplatin-based chemoradiotherapy is contraindicated, it was possible that there are some patients with good Karnofsky performance-status scores for whom any type of platinum-based chemoradiotherapy is contraindicated. The Committee accepted that the results presented for patients with Karnofsky performancestatus scores of 90% or greater indicated that cetuximab in combination with radiotherapy would be more effective than radiotherapy alone in this subgroup The Committee considered the ICER presented by the manufacturer in its original submission and the ERG s original comments. The Committee noted that the ICER of 6400 for NICE technology appraisal guidance

16 cetuximab in combination with radiotherapy versus radiotherapy alone was robust to the main sensitivity analyses. The Committee considered the ICERs presented by the manufacturer for each Karnofsky performance-status score subgroup separately. It noted that the ICERs for patients with a score of 90% or greater were favourable and similar to the overall estimate in the base case. The Committee was persuaded that although there was uncertainty about the number of patients within the subgroups who would have met the criteria to receive chemoradiotherapy, cetuximab in combination with radiotherapy is cost effective for patients with a Karnofsky performance-status score of 90% or greater and for whom chemoradiotherapy is not an option. However, for those with a Karnofsky performance-status score of 80% or less, the HR for survival did not favour cetuximab and therefore the ICERs were unfavourable. The Committee therefore was unable to recommend cetuximab for people with low performance status. Summary of the considerations 4.11 The Committee concluded that cetuximab in combination with radiotherapy is clinically and cost effective in patients with locally advanced squamous cell cancer of the head and neck who have a Karnofsky performance-status score of 90% or greater and for whom platinum-based chemoradiotherapy treatment is contraindicated. 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 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. NICE technology appraisal guidance

17 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 ( Costing report and costing template to estimate the savings and costs associated with implementation. Audit support for monitoring local practice. NICE technology appraisal guidance

18 6 Recommendations for further research 6.1 A clinical trial on radiation therapy and cisplatin with or without cetuximab in patients with stage III or stage IV head and neck cancer (RTOG-0522) is currently recruiting patients. 6.2 The Committee recommends further research on the following: Cetuximab in combination with radiotherapy compared with radiotherapy alone in patients with low Karnofsky performancestatus scores. Cetuximab in combination with radiotherapy compared with chemoradiotherapy in patients with high Karnofsky performancestatus scores. 7 Related NICE guidance Published Improving outcomes in head and neck cancers: the manual. NICE cancer service guidance (2004). Available from 8 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 The guidance on this technology will be considered for review in March Andrew Dillon Chief Executive June 2008 NICE technology appraisal guidance

19 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. Professor David Barnett Professor of Clinical Pharmacology, University of Leicester Dr David W Black Director of Public Health, Derbyshire County PCT Mr Brian Buckley Chairman, Incontact Dr Carol Campbell Senior Lecturer, University of Teesside Professor Mike Campbell Professor of Medical Statistics, University of Sheffield NICE technology appraisal guidance

20 Professor David Chadwick Professor of Neurology, Liverpool University Dr Peter Clarke Consultant Medical Oncologist, Clatterbridge Centre for Oncology, Merseyside Ms Jude Cohen Manager of Resources & Administration, United Kingdom Council for Psychotherapy (UKCP) Dr Christine Davey Senior Researcher, North Yorkshire Alliance Research and Development Unit Dr Mike Davies Consultant Physician, Manchester Royal Infirmary Mr Richard Devereaux-Phillips Public Affairs Manager, Medtronic Dr Rachel A Elliott Lord Trent Professor of Medicines and Health, University of Nottingham Mrs Eleanor Grey Lay member Dr Dyfrig Hughes Senior Research Fellow in Pharmacoeconomics, Centre for the Economics of Health and Policy in Health, University of Wales Dr Catherine Jackson Clinical Lecturer in Primary Care Medicine, Alyth Health Centre Dr Peter Jackson Clinical Pharmacologist, University of Sheffield NICE technology appraisal guidance

21 Professor Peter Jones Pro Vice Chancellor for Research & Enterprise, Professor of Statistics, Keele University Ms Rachel Lewis Practice Development Facilitator, Manchester PCT Damien Longson Consultant in Liaison Psychiatry, North Manchester General Hospital Professor Jonathan Michaels Professor of Vascular Surgery, University of Sheffield Dr Eugene Milne Deputy Medical Director, North East Strategic Health Authority Dr Simon Mitchell Consultant Neonatal Paediatrician, St Mary s Hospital, Manchester Dr Richard Alexander Nakielny Consultant Radiologist, Royal Hallamshire Hospital, Sheffield Dr Katherine Payne Health Economics Research Fellow, University of Manchester Dr Martin J Price Head of Outcomes Research, Janssen-Cilag Dr Philip Rutledge GP and Consultant in Medicines Management, NHS Lothian Mr Miles Scott Chief Executive, Bradford Teaching Hospitals NHS Foundation Trust Professor Mark Sculpher Professor of Health Economics, University of York Professor Andrew Stevens Chair of Appraisal Committee C NICE technology appraisal guidance

22 Dr Cathryn Thomas GP and Associate Professor, University of Birmingham Mr William Turner Consultant Urologist, Addenbrookes Hospital, Cambridge B NICE project team 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. Nicola Hay Technical Lead Janet Robertson Technical Adviser Chris Feinmann Project Manager NICE technology appraisal guidance

23 Appendix B: Sources of evidence considered by the Committee A The Evidence Review Group (ERG) report for this appraisal was prepared by the Centre for Health Economics, University of York and NHS Northern and Yorkshire Regional Drug and Therapeutics Centre, Newcastle. Griffin S et al. Cetuximab for the treatment of locally advanced squamous cell carcinoma of the head and neck, September 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 gave their expert views on cetuximab by providing a written statement to the Committee. Organisations listed in I, II and III were requested to submit further evidence as a result of the appeal decision. Organisations listed in I and II have the opportunity to appeal against the final appraisal determination. I Manufacturer/sponsor: Merck Pharmaceuticals UK II Professional/specialist and patient/carer groups: British Association of Head and Neck Oncologists British Association of Head and Neck Oncology Nurses British Association of Oral and Maxillofacial Surgeons Cancer Networks Pharmacists Forum (BOPA) Cancer Research UK Cancerbackup Department of Health Get A-Head Let s Face it Mouth Cancer Foundation National Association of Laryngectomee Clubs Royal College of General Practitioners Royal College of Nursing NICE technology appraisal guidance

24 Royal College of Paediatrics and Child Health Royal College of Pathologists Royal College of Physicians Medical Oncology Joint Special Committee Royal College of Radiologists Royal Pharmaceutical Society Sheffield South West PCT Welsh Assembly Government III Commentator organisations (without the right of appeal): British National Formulary Centre for Health Economics, University of York and the Regional Drug and Therapeutics Centre, Newcastle Department of Health, Social Services and Public Safety for Northern Ireland King's College Hospital Maxillofacial Unit The Head and Neck Oncology Group Medical Research Council (MRC) Clinical Trials Unit National Collaborating Centre for Cancer National Coordinating Centre for Health Technology Assessment NHS Quality Improvement 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 were also invited to comment on the ACD. Dr Nick Slevin, Consultant Clinical Oncologist, Christie Hospital NHS Trust, nominated by the Royal College of Radiologists clinical specialist Dr Kevin Harrington, Mayo Clinic College of Medicine, nominated by the Royal College of Radiologists clinical specialist (written statement only) Ms Brenda Brady, nominated by the Mouth Cancer Foundation patient expert Mrs Jean Fraser, nominated by the National Association of Laryngectomee Clubs patient expert NICE technology appraisal guidance

25 Issue date: June 2008 Quick reference guide NHS National Institute for Health and Clinical Excellence Cetuximab for the treatment of locally advanced squamous cell cancer of the head and neck Guidance 1 Cetuximab in combination with radiotherapy is recommended as a treatment option only for patients with locally advanced squamous cell cancer of the head and neck whose Karnofsky performance-status score is 90% or greater and for whom all forms of platinum-based chemoradiotherapy treatment are contraindicated. 2 Patients currently receiving cetuximab in combination with radiotherapy for the treatment of locally advanced squamous cell cancer of the head and neck who do not meet the criteria outlined in section 1 should have the option to continue therapy until they and their clinicians consider it appropriate to stop. 3 When using Karnofsky performance-status score, clinicians should be mindful of the need to secure equality of access to treatment for patients with disabilities. Clinicians should bear in mind that people with disabilities may have difficulties with activities of daily living that are unrelated to their prognosis with respect to cancer of the head and neck. In such cases clinicians should make appropriate judgements of performance status taking into account the person s usual functional capacity and requirement for assistance with activities of daily living. Implementation tools NICE has developed tools to help organisations implement this guidance (listed below). These are available on our website ( Local costing template incorporating a costing report to estimate the savings and costs associated with implementation. Audit support for monitoring local practice. NICE technology appraisal guidance 145 The guidance was developed using the NICE single technology appraisal process. NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales.

26 Further information Ordering information You can download the following documents from A quick reference guide (this document) a summary of recommendations for healthcare professionals. Understanding NICE guidance information for patients and carers. The full guidance. Details of all the evidence that was looked at and other background information. For printed copies of the quick reference guide or Understanding NICE guidance, phone NICE publications on or publications@nice.org.uk and quote: N1608 (quick reference guide) N1609 ( Understanding NICE guidance ). Related NICE guidance For information about NICE guidance that has been issued or is in development, see the website ( Improving outcomes in head and neck cancers: the manual. NICE cancer service guidance (2004). Available from Updating the appraisal This technology appraisal will be considered for review in March Information about the progress of a review will be posted on the NICE website ( This guidance represents the view of the Institute, which was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. National Institute for Health and Clinical Excellence, All rights reserved. This material may be freely reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the express written permission of the Institute. National Institute for Health and Clinical Excellence ISBN MidCity Place, 71 High Holborn, London WC1V 6NA; N k 1P Jun 08

27 Understanding NICE guidance Information for people who use NHS services Cetuximab for the treatment of locally advanced squamous cell cancer of the head and neck NICE technology appraisal guidance advises on when and how drugs and other treatments should be used in the NHS. This leaflet is about when cetuximab should be used to treat people with locally advanced squamous cell cancer of the head and neck in the NHS in England and Wales. It explains guidance (advice) from NICE (the National Institute for Health and Clinical Excellence). It is written for people with locally advanced squamous cell cancer of the head and neck but it may also be useful for their families or carers or anyone with an interest in the condition. It does not describe locally advanced squamous cell cancer of the head and neck or the treatments in detail a member of your healthcare team should discuss these with you. Some sources of further information and support are on the back page. Information about NICE technology appraisal guidance 145 Issue date: June 2008

28 This may not be the only possible treatment for locally advanced squamous cell cancer of the head and neck. Your healthcare team should talk to you about whether it is suitable for you and about other treatment options available. What has NICE said? Cetuximab in combination with radiotherapy is recommended as a possible treatment for people with locally advanced squamous cell cancer of the head and neck if: they have a Karnofsky performance-status score of 90% or more, and all forms of platinum-based chemotherapy are considered inappropriate. Healthcare professionals should not stop prescribing cetuximab in combination with radiotherapy for people who were already receiving it when the guidance was issued, but who do not fulfil the above criteria. These patients should be able to carry on taking cetuximab until they and their healthcare professionals decide that it is the right time to stop treatment. When assessing Karnofsky performance-status score, healthcare professionals should take into account any disabilities that might affect a person s ability to carry out daily activities. Locally advanced squamous cell cancer of the head and neck The cells that line parts of the body like the mouth and nose are called the epithelium. Squamous cell cancer of the head and neck is cancer of the epithelium of the mouth, nose, throat and surrounding areas. Cancer is described as locally advanced when it has spread to the surrounding tissues. Karnofsky performance status is a measure of someone s ability to carry out daily activities. A person with a score of 100% would have no signs of disease and would be able to carry out everyday tasks normally. Someone with a score of 90% would show some signs of disease, but they would still be able to carry out everyday tasks as normal. Cetuximab Cetuximab (also called Erbitux) is a drug that stops cancer cells from multiplying. It is given through a drip into a vein. 2Information about about NICE NICE technology appraisal appraisal guidance guidance 145xx

29 What does this mean for me? When NICE recommends a treatment, the NHS must ensure it is available to those people it could help, normally within 3 months of the guidance being issued. So, if you have locally advanced squamous cell cancer of the head and neck, you have a Karnofsky performance-status score of 90% or more, all forms of platinum-based chemotherapy are inappropriate for you and your doctor thinks that cetuximab is the right treatment for you, you should be able to have the treatment on the NHS. Please see if you appear to be eligible for the treatment but it is not available. If you are already taking cetuximab with radiotherapy for locally advanced squamous cell cancer of the head and neck but you do not fulfil the required criteria, you should be able to continue taking it until you and your healthcare professionals decide it is the right time to stop. Information about about NICE NICE technology appraisal guidance xx145 3

30 More information The organisations below can provide more information and support for people with locally advanced squamous cell cancer of the head and neck. Please note that NICE is not responsible for the quality or accuracy of any information or advice provided by these organisations. Cancerbackup, Get A-Head, Let s Face It, Mouth Cancer Foundation, National Association of Laryngectomee Clubs, NHS Direct online ( may be a good starting point for finding out more. Your local Patient Advice and Liaison Service (PALS) may also be able to give you further advice and support. About NICE NICE produces guidance (advice) for the NHS about preventing, diagnosing and treating different medical conditions. The guidance is written by independent experts including healthcare professionals and people representing patients and carers. They consider all the research on the disease or treatment, talk to people affected by it, and consider the costs involved. Staff working in the NHS are expected to follow this guidance. To find out more about NICE, its work and how it reaches decisions, see This leaflet and other versions of the guidance aimed at healthcare professionals are available at You can order printed copies of this leaflet from NICE publications (phone or publications@nice.org.uk and quote reference N1609). We encourage NHS and voluntary sector organisations to use text from this leaflet in their own information about locally advanced squamous cell cancer of the head and neck. National Institute for Health and Clinical Excellence MidCity Place, 71 High Holborn, London WC1V 6NA; ISBN N1609 1k 1P Jun 08 National Institute for Health and Clinical Excellence, All rights reserved. This material may be freely reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the express written permission of the Institute.

31 Tel: Ref: 2008/038 PRESS RELEASE NICE issues guidance on the use of cetuximab for the treatment of head and neck cancer The National Institute for Health and Clinical Excellence (NICE) has today (25 June 2008) published guidance on the use of cetuximab for the treatment of head and neck cancer. Cetuximab in combination with radiotherapy is recommended as a possible treatment for people with locally advanced squamous cell cancer of the head and neck if: they have a Karnofsky performance-status score of 90% or more, and all forms of platinum-based chemotherapy are considered inappropriate. Healthcare professionals should not stop prescribing cetuximab in combination with radiotherapy for people who were already receiving it when the guidance was issued, but who do not fulfil the above criteria. These patients should be able to carry on taking cetuximab until they and their healthcare professionals decide that it is the right time to stop treatment. When assessing Karnofsky performance-status score, healthcare professionals should take into account any disabilities that might affect a person s ability to carry out daily activities. Professor Peter Littlejohns, NICE Clinical and Public Health Director and Executive Lead for this guidance said: Squamous cell cancer of the head and neck is cancer of the lining of the mouth, nose, throat and surrounding areas. Our independent advisory committee has recommended cetuximab for a specific subgroup of patients for whom this treatment is both clinically and cost effective. Ends Page 1 of 2

32 Notes for editors About this appraisal 1. Karnofsky performance status is a measure of someone s ability to carry out daily activities. A person with a score of 100% would have no signs of disease and would be able to carry out everyday tasks normally. Someone with a score of 90% would show some signs of disease, but they would still be able to carry out everyday tasks as normal. About NICE 2. 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. 3. 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. Page 2 of 2

33 Cetuximab for the treatment of locally advanced squamous cell cancer of the head and neck Costing template and report Implementing NICE guidance June 2008 NICE technology appraisal guidance TA 145 TA145

34 Costing template for Cetuximab for the treatment of locally advanced squamous cell cancer of the head and neck Introduction This template aims to help organisations in England, Wales and Northern Ireland plan for the financial implications of implementing NICE technology appraisal guidance for Cetuximab for the treatment of locally advanced squamous cell cancer of the head and z neck. Estimates of both the national cost for England and local cost impact based on assumptions made about current practice and predication of how current practice change following implementation are included. You are able to modify the This costing tool is made up of the following worksheets. A title page, which can be printed as a cover for the report. 'How to use this document', including an introduction and instructions. 'Step 1. Select local population', for tailoring local cost-impact calculations as detailed in the instructions below. 'Step 2. Costing template', which provides background to estimates made and can be used to reflect local circumstances. 'Step 3. Costing report', which summarises the results. To go directly to the summary without amending local circumstances, click here 'Sensitivity analysis' indicating the impact of uncertainty in estimates and predictions. 'Where to find the guidance'. may assumptions and variables, using the instructions below, to tailor the local cost impact to your circumstances. In addition to the costing tool this technology appraisal is accompanied by the following implementation tools: audit criteria. Costing template: Cetuximab head and neck cancer

35 How to use this costing template Step 1. Select local population The template allows you to estimate the local cost of fully implementing the guidance by feeding in local population figures. To select the population, click on the tab at the bottom of the screen that says S tep 1. Select local population. Enter a description of your locality in cell A6. This description will be used on the template and summary worksheets. The arrows in the column headings allow filtering to display only selected rows (rathe r than initially select rows ). Population data are provided for the following configurations: English primary care trusts ( PCTs) in the new configuration. English strategic health authorities in the new configurations. English cancer networks (estimated gr oupings). Welsh local health boards. Northern Irish health and social care boards. To select a population of one organisation Select the row for the relevant organisation and change the figure in the % column from 0.00% to %. You can do this for mo re than one organisation at a time to reflect joint commissioning. For service providers that serve a number of different organisations You can enter varying proportions of a number of organisations. This method may be useful in a situation such as, for ex ample, United Bristol Healthcare Trust served 100% of the population of Bristol North, 90% of Bristol South and West (with 10% of patients treated elsewhere) and 20% of Bath and North East Somerset. If you know your population, or if you have more recent You can enter a single population directly into row 11. population estimates Printing local population page Because this is a very long page you may not want to print it all out. To print just a record of the population selected, without the rows that are set at 0%, do the following. Click on the down arrow to the right of the requ ired column heading. Select (Custom ) this displays the Custom autofilter box. Select Is greater than in the top left field from the drop -down menu and type 0 into the top right field. Then click the OK button. Print. To re-display all rows, cli ck on the down arrow to the right of the required column heading and select (All). Costing template: Cetuximab head and neck cancer

36 Step 2. Adapt costing template to reflect local circumstances To adapt the costing template c lick on the tab at the bottom of the screen that says Step 2. Costing template. The worksheet is divided into three sections: The left section The left section d escribes the model developed some of these fields contain references to footnotes that indicate the data source or how the assumptions ha ve been made. The middle section This section contains the model used to estimate the national cost to implement the guidance. Fi gures in this section represent the estimated national average. The right section The population selected in step 1 wil l be used for the calculations i n this section and the other variables are initially set the same as the national model. The worksheet is protected to prevent formulae being inadvertently changed, but any local circumstances. For example: shade d cell can be changed to reflect Incidence If more detailed statistics about local incidence are available, these can be used in place o f the national estimate. Drug prices These are based o n either the BNF or Drug Tariff prices the source and edition will be noted in the footnotes ; national prices exclude VAT. These can be updated to the latest prices, which could reflect local discoun ts or incorporate VAT. Activity costs The costs for activities have been based on either the health economics reports or the costs to commissioners purchasing services locally under Payment by results. The source will be noted in the footnotes. Local cir cumstances will dictate what the care pathway is, and where services are delivered. For example, stroke rehabilitation could either be based in acute or community services. Update to reflect local circumstances and costs. Costing template: Cetuximab head and neck cancer

37 Step 3. Review the costing report To view the costing report click on the tab at the bottom of the screen that says Step 3. Costing report. This worksheet summarises the national and local costing template without the detail of the calculations. It also contains information about how this tool was developed, and other costing issues relevant to the topic that should be considered. The description of the locality entered in step 1 is used in the title for the local costing report, but this cell can be upd ated independently if required. You may wish to print this sheet and use it as a briefing report to discuss the costing exercise with non -finance staff, or as part of a business case for funds for implementation. Send feedback and suggestions about this te mplate to: costing@nice.org.uk This document is written in the following context This costing template and costing report is designed to support implementation of NICE guidance, and was arrived at after careful consideration of the available data and through consulting health care and finance professionals. It is not NICE guidance. Organisations should plan for the impl ementation of guidance locally. This document can be used as an implementa tion tool during that process. It will indicate a likely cost of implementing the guidance locally, when tai lored to local circumstances. Assumptions used in this template are based on assessment of the national average. Local practice or circumstances may differ from this. The template must be adapted to reflect these differences. The costs published in this template are estimates only and are not to be taken as the Institute's view of desirable, or maximum or minimum figures. National Institute for Health and Clinical Excelle MidCity Place 71 High Holborn London WC1V 6NA nce National Institute for Health and Clinical Excellence, All rights reserved. This material may be freely reproduced for educational and not -for-profit purposes. No reproduction b y or for commercial organisations, or for commercial purposes, is allowed without the express written permission of the Institute. Costing template: Cetuximab head and neck cancer

38 Costing template for Cetuximab for the treatment of locally advanced squamous cell cancer of the head and neck Step 1. Select local population [Enter the name of your locality here] Total population for England Selected population Country Strategic health authority Primary care trust % Selected total population Selected Male Population Selected Female Population MANUAL INPUT England All PCTs All PCTs in England 0,00% England East Midlands SHA Bassetlaw PCT 0,00% England East Midlands SHA Derby City PCT 0,00% England East Midlands SHA Derbyshire County PCT 0,00% England East Midlands SHA Leicester City PCT 0,00% England East Midlands SHA Leicestershire County and Rutland PCT 0,00% England East Midlands SHA Lincolnshire PCT 0,00% England East Midlands SHA Northamptonshire PCT 0,00% England East Midlands SHA Nottingham City PCT 0,00% England East Midlands SHA Nottinghamshire County PCT 0,00% England East of England SHA Bedfordshire PCT 0,00% England East of England SHA Cambridgeshire PCT 0,00% England East of England SHA East and North Hertfordshire PCT 0,00% England East of England SHA Great Yarmouth and Waveney PCT 0,00% England East of England SHA Luton PCT 0,00% England East of England SHA Mid Essex PCT 0,00% England East of England SHA Norfolk PCT 0,00% England East of England SHA North East Essex PCT 0,00% England East of England SHA Peterborough PCT 0,00% England East of England SHA South East Essex PCT 0,00% England East of England SHA South West Essex PCT 0,00% England East of England SHA Suffolk PCT 0,00% England East of England SHA West Essex PCT 0,00% England East of England SHA West Hertfordshire PCT 0,00% England London SHA Barking and Dagenham PCT 0,00% England London SHA Barnet PCT 0,00% England London SHA Bexley Care Trust 0,00% England London SHA Brent Teaching PCT 0,00% England London SHA Bromley PCT 0,00% England London SHA Camden PCT 0,00% England London SHA City and Hackney Teaching PCT 0,00% England London SHA Croydon PCT 0,00% England London SHA Ealing PCT 0,00% England London SHA Enfield PCT 0,00% England London SHA Greenwich Teaching PCT 0,00% England London SHA Hammersmith and Fulham PCT 0,00% England London SHA Haringey Teaching PCT 0,00% England London SHA Harrow PCT 0,00% England London SHA Havering PCT 0,00% England London SHA Hillingdon PCT 0,00% England London SHA Hounslow PCT 0,00% England London SHA Islington PCT 0,00% England London SHA Kensington and Chelsea PCT 0,00% England London SHA Kingston PCT 0,00% England London SHA Lambeth PCT 0,00% England London SHA Lewisham PCT 0,00% England London SHA Newham PCT 0,00% England London SHA Redbridge PCT 0,00% England London SHA Richmond and Twickenham PCT 0,00% England London SHA Southwark PCT 0,00% England London SHA Sutton and Merton PCT 0,00% England London SHA Tower Hamlets PCT 0,00% England London SHA Waltham Forest PCT 0,00% England London SHA Wandsworth PCT 0,00% England London SHA Westminster PCT 0,00% England North East SHA County Durham PCT 0,00% England North East SHA Darlington PCT 0,00% England North East SHA Gateshead PCT 0,00% England North East SHA Hartlepool PCT 0,00% England North East SHA Middlesbrough PCT 0,00% England North East SHA Newcastle PCT 0,00% England North East SHA North Tees PCT 0,00% England North East SHA North Tyneside PCT 0,00% England North East SHA Northumberland Care Trust 0,00% England North East SHA Redcar and Cleveland PCT 0,00% England North East SHA South Tyneside PCT 0,00% England North East SHA Sunderland Teaching PCT 0,00% Costing template: Cetuximab head and neck cancer

39 England North West SHA Ashton, Leigh and Wigan PCT 0,00% England North West SHA Blackburn with Darwen PCT 0,00% England North West SHA Blackpool PCT 0,00% England North West SHA Bolton PCT 0,00% England North West SHA Bury PCT 0,00% England North West SHA Central and Eastern Cheshire PCT 0,00% England North West SHA Central Lancashire PCT 0,00% England North West SHA Cumbria PCT 0,00% England North West SHA East Lancashire PCT 0,00% England North West SHA Halton and St Helens PCT 0,00% England North West SHA Heywood, Middleton and Rochdale PCT 0,00% England North West SHA Knowsley PCT 0,00% England North West SHA Liverpool PCT 0,00% England North West SHA Manchester PCT 0,00% England North West SHA North Lancashire PCT 0,00% England North West SHA Oldham PCT 0,00% England North West SHA Salford PCT 0,00% England North West SHA Sefton PCT 0,00% England North West SHA Stockport PCT 0,00% England North West SHA Tameside and Glossop PCT 0,00% England North West SHA Trafford PCT 0,00% England North West SHA Warrington PCT 0,00% England North West SHA Western Cheshire PCT 0,00% England North West SHA Wirral PCT 0,00% England South Central SHA Berkshire East PCT 0,00% England South Central SHA Berkshire West PCT 0,00% England South Central SHA Buckinghamshire PCT 0,00% England South Central SHA Hampshire PCT 0,00% England South Central SHA Isle of Wight NHS PCT 0,00% England South Central SHA Milton Keynes PCT 0,00% England South Central SHA Oxfordshire PCT 0,00% England South Central SHA Portsmouth City Teaching PCT 0,00% England South Central SHA Southampton City PCT 0,00% England South East Coast SHA Brighton and Hove City PCT 0,00% England South East Coast SHA East Sussex Downs and Weald PCT 0,00% England South East Coast SHA Eastern and Coastal Kent PCT 0,00% England South East Coast SHA Hastings and Rother PCT 0,00% England South East Coast SHA Medway PCT 0,00% England South East Coast SHA Surrey PCT 0,00% England South East Coast SHA West Kent PCT 0,00% England South East Coast SHA West Sussex PCT 0,00% England South West SHA Bath and North East Somerset PCT 0,00% England South West SHA Bournemouth and Poole PCT 0,00% England South West SHA Bristol PCT 0,00% England South West SHA Cornwall and Isles Of Scilly PCT 0,00% England South West SHA Devon PCT 0,00% England South West SHA Dorset PCT 0,00% England South West SHA Gloucestershire PCT 0,00% England South West SHA North Somerset PCT 0,00% England South West SHA Plymouth Teaching PCT 0,00% England South West SHA Somerset PCT 0,00% England South West SHA South Gloucestershire PCT 0,00% England South West SHA Swindon PCT 0,00% England South West SHA Torbay Care Trust 0,00% England South West SHA Wiltshire PCT 0,00% England West Midlands SHA Birmingham East and North PCT 0,00% England West Midlands SHA Coventry Teaching PCT 0,00% England West Midlands SHA Dudley PCT 0,00% England West Midlands SHA Heart of Birmingham Teaching PCT 0,00% England West Midlands SHA Herefordshire PCT 0,00% England West Midlands SHA North Staffordshire PCT 0,00% England West Midlands SHA Sandwell PCT 0,00% England West Midlands SHA Shropshire County PCT 0,00% England West Midlands SHA Solihull Care Trust 0,00% England West Midlands SHA South Birmingham PCT 0,00% England West Midlands SHA South Staffordshire PCT 0,00% England West Midlands SHA Stoke On Trent PCT 0,00% England West Midlands SHA Telford and Wrekin PCT 0,00% England West Midlands SHA Walsall Teaching PCT 0,00% England West Midlands SHA Warwickshire PCT 0,00% England West Midlands SHA Wolverhampton City PCT 0,00% England West Midlands SHA Worcestershire PCT 0,00% England Yorkshire and the Humber SHA Barnsley PCT 0,00% England Yorkshire and the Humber SHA Bradford and Airedale PCT 0,00% England Yorkshire and the Humber SHA Calderdale PCT 0,00% England Yorkshire and the Humber SHA Doncaster PCT 0,00% England Yorkshire and the Humber SHA East Riding Of Yorkshire PCT 0,00% England Yorkshire and the Humber SHA Hull PCT 0,00% England Yorkshire and the Humber SHA Kirklees PCT 0,00% England Yorkshire and the Humber SHA Leeds PCT 0,00% England Yorkshire and the Humber SHA North East Lincolnshire PCT 0,00% England Yorkshire and the Humber SHA North Lincolnshire PCT 0,00% England Yorkshire and the Humber SHA North Yorkshire and York PCT 0,00% England Yorkshire and the Humber SHA Rotherham PCT 0,00% England Yorkshire and the Humber SHA Sheffield PCT 0,00% England Yorkshire and the Humber SHA Wakefield District PCT 0,00% England East Midlands SHA All PCTs in East Midlands SHA 0,00% England East of England SHA All PCTs in East of England SHA 0,00% England London SHA All PCTs in London SHA 0,00% England North East SHA All PCTs in North East SHA 0,00% England North West SHA All PCTs in North West SHA 0,00% England South Central SHA All PCTs in South Central SHA 0,00% England South East Coast SHA All PCTs in South East Coast SHA 0,00% England South West SHA All PCTs in South West SHA 0,00% England West Midlands SHA All PCTs in West Midlands SHA 0,00% England Yorkshire and the Humber SHA All PCTs in Yorkshire and the Humber SHA 0,00% Costing template: Cetuximab head and neck cancer

40 Wales Wales Anglesey LHB 0,00% Wales Wales Blaenau Gwent LHB 0,00% Wales Wales Bridgend LHB 0,00% Wales Wales Caerphilly LHB 0,00% Wales Wales Cardiff LHB 0,00% Wales Wales Carmarthenshire LHB 0,00% Wales Wales Ceredigion LHB 0,00% Wales Wales Conwy LHB 0,00% Wales Wales Denbighshire LHB 0,00% Wales Wales Flintshire LHB 0,00% Wales Wales Gwynedd LHB 0,00% Wales Wales Merthyr Tydfil LHB 0,00% Wales Wales Monmouthshire LHB 0,00% Wales Wales Neath Port Talbot LHB 0,00% Wales Wales Newport LHB 0,00% Wales Wales Pembrokeshire LHB 0,00% Wales Wales Powys LHB 0,00% Wales Wales Rhondda Cynon Taff LHB 0,00% Wales Wales Swansea LHB 0,00% Wales Wales Torfaen LHB 0,00% Wales Wales Vale Of Glamorgan LHB 0,00% Wales Wales Wrexham LHB 0,00% Wales Wales All LHBs in Wales 0,00% Northern Ireland Northern Ireland Eastern Board 0,00% Northern Ireland Northern Ireland Northern Board 0,00% Northern Ireland Northern Ireland Southern Board 0,00% Northern Ireland Northern Ireland Western Board 0,00% Northern Ireland Northern Ireland All Health Boards in Northern Ireland 0,00% Cancer Network Cancer 3 Counties 0,00% Cancer Network Cancer Anglia 0,00% Cancer Network Cancer Arden 0,00% Cancer Network Cancer Avon, Somerset & Wiltshire 0,00% Cancer Network Cancer Central South Coast 0,00% Cancer Network Cancer Derby/Burton 0,00% Cancer Network Cancer Dorset 0,00% Cancer Network Cancer Essex 0,00% Cancer Network Cancer Greater Manchester & Cheshire 0,00% Cancer Network Cancer Greater Midlands 0,00% Cancer Network Cancer Humber & Yorkshire 0,00% Cancer Network Cancer Kent & Medway 0,00% Cancer Network Cancer Lancashire & South Cumbria 0,00% Cancer Network Cancer Leicestershire, Northamptonshire & Rutland 0,00% Cancer Network Cancer Merseyside and Cheshire 0,00% Cancer Network Cancer Mid Trent 0,00% Cancer Network Cancer Mount Vernon 0,00% Cancer Network Cancer North East London 0,00% Cancer Network Cancer North London 0,00% Cancer Network Cancer North of England 0,00% Cancer Network Cancer North Trent 0,00% Cancer Network Cancer Pan Birmingham 0,00% Cancer Network Cancer Peninsula 0,00% Cancer Network Cancer South East London 0,00% Cancer Network Cancer South West London 0,00% Cancer Network Cancer Surrey, West Sussex & Hampshire 0,00% Cancer Network Cancer Sussex 0,00% Cancer Network Cancer Thames Valley 0,00% Cancer Network Cancer West London 0,00% Cancer Network Cancer Yorkshire 0,00% Cardiac Network Cardiac Anglia 0,00% Cardiac Network Cardiac Avon, Gloucestershire & Wiltshire 0,00% Cardiac Network Cardiac Bedfordshire & Hertfordshire 0,00% Cardiac Network Cardiac Birmingham, Sandwell & Solihull 0,00% Cardiac Network Cardiac Black Country 0,00% Cardiac Network Cardiac Cheshire & Merseyside 0,00% Cardiac Network Cardiac Coast to Coast 0,00% Cardiac Network Cardiac Coventry & Warwickshire 0,00% Cardiac Network Cardiac Dorset & Somerset 0,00% Cardiac Network Cardiac East Surrey & North Sussex 0,00% Cardiac Network Cardiac Essex 0,00% Cardiac Network Cardiac Greater Manchester & Cheshire 0,00% Cardiac Network Cardiac Herefordshire & Worcestershire 0,00% Cardiac Network Cardiac Kent 0,00% Cardiac Network Cardiac Lancashire & South Cumbria 0,00% Cardiac Network Cardiac Leicestershire, Northamptonshire & Rutland 0,00% Cardiac Network Cardiac North Central London 0,00% Cardiac Network Cardiac North East London 0,00% Cardiac Network Cardiac North East Yorkshire & Northern Leicestershire 0,00% Cardiac Network Cardiac North Trent 0,00% Cardiac Network Cardiac North West London 0,00% Cardiac Network Cardiac Northern 0,00% Cardiac Network Cardiac Peninsula 0,00% Cardiac Network Cardiac Shropshire & Staffordshire 0,00% Cardiac Network Cardiac South Central 0,00% Cardiac Network Cardiac South East London 0,00% Cardiac Network Cardiac South West London 0,00% Cardiac Network Cardiac Sussex Heart Network 0,00% Cardiac Network Cardiac Trent 0,00% Cardiac Network Cardiac West Surrey 0,00% Cardiac Network Cardiac West Yorkshire 0,00% Information is provided in the new configurations for PCTs from October Information for the old configurations is no longer provided by the Information Centre so we can no longer provide it in the templates. Source of data: The Information Centre for health and social care has produced updated population figures at strategic health authority (SHA) and primary care organisation (PCO) level for England and local health board (LHB) level for Wales. The data were collected in 2007 for GP-relevant populations as at April The data have been constrained to the Office for National Statistics 2006 mid-year population estimates based on the 2001 Census but do not include armed forces and some prisoners. Source of data: Northern Ireland Statistics and Research Agency (NISRA) population statistics 'Table 2.5 Estimated population by sex, quinary age group and health board, 2005.' Costing template: Cetuximab head and neck cancer

41 Costing template for Cetuximab for the treatment of locally advanced squamous cell cancer of the head and neck Step 2. Costing template Cost for selected population using standard assumptions Cost for selected population using local assumptions England [Enter the name of your locality here] [Enter the name of your locality here] Notes Description Unit cost ( ) Units Total cost ( ) Unit cost ( ) Units Total cost ( ) Unit cost ( ) Units Total cost ( ) Blue cells should be amended to reflect local circumstances *1 Total male population *1 Total female population *2 Estimated incidence of male head and neck cancer 0,022% 0,022% 0,022% *2 Estimated incidence of female head and neck cancer 0,009% 0,009% 0,009% *2 Total number of male cases of head and neck cancer *2 Total number of female cases of head and neck cancer Total cases of head and neck cancer *3 Proportion of patients with a Karnofsky score greater than or equal to 90% and a contraindication to Platinum chemotherapy 8,00% 8,00% 8,00% Number of new patients benefiting from cetuximab with radiotherapy Cost of providing cetuximab per patient: Number of weeks per treatment *4 Drug cost: *5 Initial dose 955, ,50 955, ,50 955, ,50 *6 Subsequent weekly doses 682, ,50 682, ,50 682, ,50 *7 Initial Administration costs 309, ,00 309, ,00 309, ,00 *8 Subsequent Administration costs 255, ,00 255, ,00 255, ,00 Total additional cost per patient of receiving cetuximab in addition to radiotherapy Estimated additional annual cost of prescribing cetuximab in addition to radiotherapy. 309, ,00 309, ,00 309, , Note Description *1 See cells E7-H7 on Step 1 for full description of populations used in the model *2 Sourced from Merk Pharmaceutical's single technology appraisal submission *3 Clinical expert opinion *4 The drug costs per a vial containing 20 ml of 5mg/ml. The dose is measured per m² of body surface area. Body surface areas range from 1.6m² to 1.8m² and so I have assumed an average of 1.7m² *5 The initial dose is 400mg/m² *6 A course of treatment is prescribed at 250 mg/m² and can range between 2 and 8 weeks. The base costing assumes 6 weeks based on feedback that this would be a typical regime within the NHS. *7 Administration costs are based on the national reference costs for 2007 for an inpatient delivery of parenteral Chemotherapy at first attendance *8 Administration costs are based on the national reference costs for 2007 for an inpatient delivery of subsequent elements of a chemotherapy cycle Costing template: Cetuximab head and neck cancer

42 Costing template for Cetuximab for the treatment of locally advanced squamous cell cancer of the head and neck Costing report Cost of fully implementing the guidance nationally and for [Enter the name of your locality here] Introduction Technology appraisals are core standards within the Department of Health s document Standards for better health and, unless otherwise directed by the Department of Health, NHS bodies should make funding available for treat ments recommended by NICE within 3 months of publication of the guidance. This document supports the implementation of the guidance. It replaces the section Implications for the NHS in the full guidance that has appeared in previously published technology appraisals. The costing template can be used to estimate both the national and local cost implications of implementing the guidance. By varying the assumptions a nd feeding in data that reflect local circumstances, the local cost implications can be calculated. The national costing report illustrates the broader implications for the NHS. It is derived from the same template, but using n ational data. A summary for each of these reports is shown below. How the costing template was developed The development of the costing template for national and local use followed a structured approach which involved: carrying out background research into the appraisal content, current clinical practice, published information and available data gathering expert opinion developing a costing model to be used to estimate the cost of implementation testing the model, including the assumptions and outcomes developing the template and report based on the costing model. Background of this technology appraisal Cetuximab in combination with radiotherapy is recommended as a treatment option only for patients with locally advanced squamous cell cancer of the head and neck whose Karnofsky performance -status score is 90% or gre ater and for whom all forms of platinum - based chemoradiotherapy treatment are contraindicated. Patients currently receiving cetuximab in combination with radiotherapy for the treatment of locally advanced squamous cell cancer of the head and neck who do n ot meet the criteria outlined in section 1.1 of the final appraisal determination should have the option to continue therapy until they and their clinicians consider it appropriate to stop. Cetuximab (Erbitux, Merck Pharmaceuticals) is a chimeric immunoglo bulin G monoclonal antibody that competes for epidermal growth factor receptor (EGFR) binding sites on the external surface of the cell membrane. Binding of cetuximab to EGFR prevents activation of tyrosine kinase within cells, eventually resulting in apop tosis. Costing template: Cetuximab head and neck cancer