Horizon Scanning Technology Briefing

National Ixabepilone for locally Horizon advanced or metastatic Scanning Centre

August 2006

This technology briefing is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes. National Horizon Scanning Centre News on emerging technologies in healthcare Ixabepilone for locally advanced or metastatic breast cancer

Target group • Locally advanced or metastatic breast cancer (MBC).

Technology description Ixabepilone (BMS-247550, azaepothilone B) is an B analogue which is reported to evade the resistance mechanisms of and other cytotoxic drugs. Ixabepilone is expected to be used either as a monotherapy or in combination with , for patients who have failed and therapy, and for some who have failed capecitabine therapy. Ixabepilone is given at a dose of 40mg/m2 IV over 3 hours on day 1 followed by 40mg/m2 IV every 3 weeks.

Ixabepilone has been evaluated in phase II trials for other stages of breast cancer and other tumour types including pancreatic, renal cell and non-small cell lung cancer.

Innovation and/or advantages Ixabepilone is the first of a new class of antineoplastic agents and if licensed, could provide a further treatment option for patients.

Developer Bristol-Myers Squibb.

Purpose Diagnosis or identification of Investigation, assessment or Susceptibility testing for identifying disease staging of known disease risk of disease Prevention e.g. immunisation, Screening programme or tests to ; Individual treatment e.g. drug, public health programme identify latent or early disease device, procedure, radiotherapy Continuous therapy e.g. dialysis, Patient management and Rehabilitation life support pathways of care Service delivery changes Other:

Place of use Home care e.g. home dialysis Community or residential care e.g. Primary care e.g. used by GPs or district nurses, physio practice nurses ; Secondary care e.g. general, ; Tertiary care e.g. highly specialist Emergency care e.g. paramedic non-specialist hospital services or hospital services, trauma care General public e.g. over the Other: counter

Stage of development and availability in EU/UK ; Phase III clinical trials or Pre-registration in EU (drugs) CE marked, but not yet launched equivalent or available in UK ; Licence or CE mark application Licence or CE mark application in Launch or use in UK/EU likely in UK/EU likely within 12 months UK/EU likely within 24 months within 12 months ; Launch or use in UK/EU likely Established product, but this is a Other: within 24 months new indication in development

NHS or Government priority area: ; Cancer Cardiovascular disease Children Diabetes Chronic conditions Mental health Older people Public health Renal disease Women’s health None identified Other:

Aug 2006 2 National Horizon Scanning Centre News on emerging technologies in healthcare Relevant guidance • SIGN clinical guideline published in 20051. • NICE breast cancer service guideline published in 20022. • NICE clinical guideline on the diagnosis and treatment of breast cancer in progress (due July 2008). • Published NICE guidance for MBC includes: and 20013; 20024; tratuzumab 20025; capecitabine 20036. • NICE appraisals for MBC in progress include , due October 2006.

Clinical need and burden of disease In 2002 there were 37,134 new cases of breast cancer diagnosed in England and Wales7 and in 2003 there were 11,189 deaths8.

Advanced and MBC are defined by clinical staging based on the tumour, node and staging system, falling within stage III and stage IV. Between 16% and 20% of women presenting with breast cancer have advanced disease with distant metastases (5,940 to 7,430 women). In 2002 NICE estimated that around 50% of those presenting with early or localised breast cancer will eventually develop MBC4. Therefore, between 20,790 to 23,030 patients may be eligible for treatment with ixabepilone.

Existing comparators and treatments • First-line systemic therapy for oestrogen receptor-negative disease is (usually an anthracycline based regimen or a combination of , and ). • Hormone manipulation therapy for oestrogen receptor positive tumours. • Following disease progression on an anthracycline, patients will normally receive a taxane, then capecitabine or vinorelbine. • Tratuzimab is given in combination with the chemotherapy drugs Taxol or Taxotere to people with advanced breast cancer. It may also be given on its own to people with advanced breast cancer who have already received at least two courses of chemotherapy9.

Aug 2006 3 National Horizon Scanning Centre News on emerging technologies in healthcare Efficacy and safety

Trial name or code CA163-46 CA163-48 Sponsor BMS BMS Status Ongoing Ongoing Location Multi-centre (including UK) Multi-centre (including UK) Design - randomised, Phase III, randomised, open label. Phase III, randomised open label controlled, un-controlled, Ixabepilone plus capecitabine Ixabepilone plus capecitabine case-control, case series versus capecitabine alone. versus capecitabine alone. Participants in trial – n=750. Locally advanced or n=1200. Locally advanced or number, description, trial metastatic breast cancer metastatic breast cancer schedule e.g. placebo or previously treated or resistant to previously treated or resistant to comparator anthracycline and resistant to anthracycline and resistant to taxanes. Capecitabine (1000mg/m2 taxanes. Capecitabine orally twice daily for 14 days (1000mg/m2 orally twice daily for followed by 7 day rest) plus 14 days followed by 7 day rest) ixabepilone 40mg/m2 IV over 3 plus ixabepilone 40mg/m2 IV over hours on day one, repeated every 3 3 hours on day one, repeated weeks. Compared to capecitabine every 3 weeks. Compared to (1250mg/m2 orally twice daily for capecitabine (1250mg/m2 orally 14 days followed by 7 day rest), twice daily for 14 days followed repeated every 3 weeks. by 7 day rest), repeated every 3 weeks Follow-up Until death. Until death. Primary outcome Time to progression. Overall survival Secondary outcomes Overall survival; response rate and Time to progression; response duration of response; quality of rate and duration of response; life; safety. quality of life; safety. Expected reporting date Unknown Unknown

Several phase II, open label, single-arm trials have reported, one by journal article10 and others by conference abstract11, 12, 13.

Estimated cost and cost impact The cost of ixabepilone is yet to be determined.

Potential or intended impact – speculative

Patients Reduced morbidity ; Reduced mortality or increased ; Improved quality of life for survival patients and/or carers Quicker or more accurate Earlier identification of disease Changed pathway of care or diagnosis outcome

Services Increased use e.g. length of stay, Service reorganisation required Staff or training required out-patient visits Decreased use e.g. shorter length of stay, reduced referrals

Costs Increased unit cost compared to Increased costs: more patients Increased costs: capital alternative coming for treatment investment needed ; Unknown:

Aug 2006 4 National Horizon Scanning Centre News on emerging technologies in healthcare References

1 Scottish Intercollegiate Guidelines Network. Management of breast cancer in women. Guideline 84, December 2005 2 Improving outcomes in breast cancer, Cancer service Guidance, National Institute for Health and Clinical Excellence, August 2002 3 National Institute for Health and Clinical Excellence. Guidance on the use of taxanes for the treatment of breast cancer, September 2001; Technology Appraisal Guidance number 30. 4 National Institute for Health and Clinical Excellence. Guidance on the use of vinorelbine for the treatment of advanced breast cancer, December 2002; Technology Appraisal Guidance number 54. 5 National Institute for Health and Clinical Excellence. Guidance on the use of trastuzumab for the treatment of advanced breast cancer. March 2002; Technology Appraisal Guidance number 34. 6 National Institute for Health and Clinical Excellence. Guidance on the use of capecitabine for the treatment of locally advanced or metastatic breast cancer, May 2003; Technology Appraisal Guidance number 62. 7 Cancer Research UK, Cancer Stats Incidence – UK, 2006. 8 Cancer Research UK, Cancer Stats Mortality – UK, 2005. 9 Cancerbackup Hhttp://www.cancerbackup.org.uk/cancertype/breast/treatment/herceptinH (accessed on 25/09/06). 10 Low JA, Wedam SB, Lee JJ et al. A phase 2 of ixabepilone (BMS-247550), an epothilone B analog, in metastatic and locally advanced breast cancer. Journal of Clinical Oncology. 23 (12): 2726-34. April 2005 11 Roche HH, Cure H, Bunnell C et al. A phase II study of epothilone analog BMS-247550 in patients (pts) with metastatic breast cancer (MBC) previously treated with an anthracycline. American Society of Clinical Oncology annual meeting . Abstract 69, 2003. 12 Conte P, Thomas E, Martin M et al. Phase II study of ixabepilone in patients (pts) with taxane-resistant metastatic breast cancer (MBC): Final report. American Society of Clinical Oncology annual meeting. Abstract 10505, 2006. 13 Thomas E, Perez E.A, Mukhopadhyay P et al. Phase II trial of ixabepilone in patients with metastatic breast cancer (MBC) who are resistant to an anthracycline, a taxane and capecitabine. American Society of Clinical Oncology annual meeting. Abstract 660, 2006.

The National Horizon Scanning Centre is funded by the Research and Development Division of the Department of Health, England

The National Horizon Scanning Centre, Department of Public Health and Epidemiology University of Birmingham, Edgbaston, Birmingham, B15 2TT, England Tel: +44 (0)121 414 7831 Fax +44 (0)121 414 2269 www.pcpoh.bham.ac.uk/publichealth/horizon

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