National Horizon Scanning Centre

Larotaxel for advanced pancreatic cancer: recurrent and/or metastatic - second line

April 2008

This technology summary 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.

The National Horizon Scanning Centre Research Programme is part of the National Institute for Health Research April 2008 National Horizon Scanning Centre News on emerging technologies in healthcare

Larotaxel for advanced pancreatic cancer: recurrent and/or metastatic - second line

Target group • Pancreatic cancer: advanced, recurrent and/or metastatic – second line.

Technology description Larotaxel is a third-generation , which binds to tubulin, halting mitosis and causing cell death. Larotaxel has a lower affinity for P-glycoprotein than , which may overcome tumour resistance to . Larotaxel is administered at 90 mg/m2 by intravenous infusion (iv) every 3 weeks.

Larotaxel is in phase III clinical trials for bladder cancer, phase II trials for HER2- positive advanced breast cancer (in combination with trastuzumab) and phase I/II trial for advanced breast cancer (in combination with ).

Innovation and/or advantages Larotaxel may improve survival in this patient group, which has a very poor prognosis.

Developer Sanofi-Aventis.

Availability, launch or marketing dates, and licensing plans: In phase III clinical trials.

NHS or Government priority area: This topic relates to the NHS Cancer Plan (2000).

Relevant guidance • NICE technology appraisal. for the treatment of pancreatic cancer. 20011. • Proposed NICE technology appraisal – out for consultation. Capecitabine for advanced pancreatic cancer. • Pancreatic Section of the British Society of Gastroenterology, Pancreatic Society of Great Britain and Ireland, Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, Royal College of Pathologists, Special Interest Group for Gastro- Intestinal Radiology. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. 20052.

Clinical need and burden of disease Pancreatic cancer is the eighth most common cancer in the UK and the sixth most common cause of death from cancer3. There were 6,655 patients diagnosed with pancreatic cancer in 2004 in England and Wales4, and 6,462 registered deaths from pancreatic cancer in 20055. The one-year and five-year survival rates for people diagnosed in 2001 were 12-13% and 2% respectively6. An estimated 80% of patients have locally advanced or metastatic disease at diagnosis. The proportion who receive first-line is unknown.

Existing comparators and treatments • Gemcitabine iv

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• 5- iv • Capecitabine - unlicensed

Efficacy and safety

Trial code NCT004172097 PAPRIKA: Larotaxel vs 5-FU; phase III. Sponsor Sanofi-Aventis Status Ongoing Location USA, Europe, UK. Design Randomised, open label. Participants in trial n=400; adults; advanced pancreatic cancer, non-operable in a curative intent, locally recurrent or metastatic; previously treated with gemcitabine hydrochloride. Randomised to larotaxel 90 mg/m2 iv every 3 weeks vs 5-FU iv every 3 weeks. Primary outcome Overall survival (OS) Secondary outcomes Progression free survival (PFS); overall response rate (ORR); clinical benefit based on measurement of tumour related symptoms; safety and efficacy. Expected reporting date Study started in December 2006.

Estimated cost and cost impact The cost of larotaxel has not been determined.

Potential or intended impact – speculative

Patients Reduced morbidity ; Reduced mortality or increased Improved quality of life for patients survival and/or carers Quicker, earlier or more accurate Other: None identified diagnosis or identification of disease

Services ; Increased use – therapy Service reorganisation required Staff or training required administration, management of adverse effects Decreased use Other: Non identified

Costs Increased unit cost compared to Increased costs: more patients Increased costs: capital alternative coming for treatment investment needed ; New costs: drug and Savings: Other: administration costs

References

1 National Institute for Health and Clinical Excellence (NICE). Pancreatic Cancer – Gemcitabine. Technology appraisal 25. May 2001 2 Pancreatic Section of the British Society of Gastroenterology, Pancreatic Society of Great Britain and Ireland, Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, Royal College of Pathologists, Special Interest Group for Gastro-Intestinal Radiology. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Gut 2005;54:1-16

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3 Ward S, Morris E, Bansback N et al. A rapid and systematic review of the clinical effectiveness and cost- effectiveness of gemcitabine for the treatment of pancreatic cancer. Health Technology Assessment 2001;Vol. 5:No. 24. Available at: http://www.ncchta.org/execsumm/summ524.shtml (accessed 8.2.08). 4 Cancer Research UK, Cancer incidence stats. (accessed 8.2.08). http://info.cancerresearchuk.org/cancerstats/incidence/site/?a=5441 5 Cancer Research UK, Cancer mortality stats. (accessed 8.2.08). http://info.cancerresearchuk.org/cancerstats/mortality/siteandUKcountry/?a=5441 6 Cancer Research UK, Cancer survival stats. (accessed 8.2.08). http://info.cancerresearchuk.org/cancerstats/survival/siteandsex/?a=5441 7 Clinical trials. Larotaxel compared to continuous administration of 5-FU in advanced pancreatic cancer patients previously treated with a gemcitabine-containing regimen (PAPRIKA). Available at: http://clinicaltrials.gov/ct2/show/NCT00417209?term=NCT00417209&rank=1 (Accessed 25/4/08).

The National Institute for Health Research National Horizon Scanning Centre Research Programme is funded by the Department of Health. The views expressed in this publication are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health

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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