Cabazitaxel (XRP-6258)
`for hormone refractory, metastatic
`prostate cancer – second line after
`docetaxel
`
`April 2009
`
`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
`
`
`
`
`
`
`AVENTIS EXHIBIT 2078
`Mylan v. Aventis, IPR2016-00712
`
`

`
`April 2009
`
`
`
`National Horizon Scanning Centre
`
`
`News on emerging technologies in healthcare
`Cabazitaxel (XRP-6258) for hormone refractory, metastatic
`prostate cancer – second line after docetaxel
`
`
`Target group
`• Hormone refractory prostate cancer (HRPC): metastatic – second line; after
`docetaxel-based treatment.
`
`
`Technology description
`Cabazitaxel (XRP-6258) is a taxane anti-neoplastic agent. It works by disrupting the
`microtubular network that is essential for mitotic and interphase cellular functions and
`causes inhibition of cell division and cell death. Cabazitaxel in combination with
`prednisone is intended to provide a further treatment option for patients with progressive
`disease following or during docetaxel-based treatment. Cabazitaxel is administered by
`intravenous (IV) infusion at 25mg/m2 every 3 weeks.
`
`Innovation and/or advantages
`There is no approved agent for men with metastatic HRPC who have progressed during
`or after a first-line chemotherapy treatment. Cabazitaxel has shown a promising safety
`profile and activity in patients progressing after docetaxel therapy.
`
`Developer
`Sanofi-aventis.
`
`
`Availability, launch or marketing dates, and licensing plans:
`In phase III clinical trials.
`
`
`NHS or Government priority area
`This topic is relevant to the NHS Cancer Plan (2000) and Cancer Reform Strategy (2007).
`
`
`Relevant guidance
`• NICE technology appraisal. Docetaxel for the treatment of hormone refractory
`metastatic prostate cancer. 20061.
`• NICE clinical guideline. Prostate cancer: diagnosis and treatment. 20082.
`• NICE cancer service guidance. Improving outcomes in urological cancers - Manual.
`20023.
`• NICE interventional procedure guidance. High dose rate brachytherapy for prostate
`cancer. 20064.
`• NICE interventional procedure guidance. Cryotherapy as a primary treatment for
`prostate cancer. 20055.
`• NICE interventional procedure guidance. Low dose rate brachytherapy for localised
`prostate cancer. 20056.
`• NICE interventional procedure guidance. Cryotherapy for recurrent prostate cancer.
`20057.
`• NICE interventional procedure guidance. High-intensity focused ultrasound for
`prostate cancer. 20058.
`
` •
`
` Department of Health Service guideline. Advice on the development of low dose rate
`(permanent seed implant) brachytherapy services for localised prostate cancer in
`England. 20069.
`• The Royal College of Pathologists. Service guidance. Dataset for tumours of the
`urinary collecting system (Renal pelvis, ureter, bladder and urethra). 200710.
`
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`April 2009
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`National Horizon Scanning Centre
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`News on emerging technologies in healthcare
`• European Association on Prostate Cancer. Guidelines on prostate cancer. 200711.
`
`Clinical need and burden of disease
`Prostate cancer is the most common cancer diagnosed in men in the UK, with 31,135 new
`cases registered in 2005 in England and Wales12. More than 60% of cases are diagnosed
`in men over the age of 70. There were 9,052 registered deaths from prostate cancer in
`England and Wales in 200613, accounting for approximately 13% of male cancer deaths.
`It is estimated that most of these deaths occur in patients with HRPC1, although
`epidemiological data for HRPC is limited. Metastatic disease occurs in 55-60% of
`prostate cancer patients, for whom androgen deprivation is the main treatment. However,
`this is essentially palliative and all patients will eventually become resistant to hormone
`therapy at which point the prognosis becomes extremely poor (median survival 7-15
`months14).
`
`Existing comparators and treatments
`The aim of treatment for men with metastatic HRPC that has progressed during or after a
`docetaxel-based treatment, is to improve symptoms, slow progression of the disease and
`prolong life. Clinical management is acknowledged to be multimodal rather than
`sequential, and patients may receive a combination of palliative treatments1.
`
`Management options include:
`• Additional hormonal therapy (e.g. diethylstilbestrol).
`• Mitoxantrone with or without steroids - widely used for patients who are fit for
`chemotherapy (not licensed for this indication).
`• Docetaxel (Taxotere) re-challenge in patients initially responsive to docetaxel.
`
`Efficacy and safety
`
`
`
`
`Trial
`
`Sponsor
`Status
`Location
`Design
`Participants and
`schedule
`
`
`Follow-up
`Primary
`outcome
`Secondary
`outcomes
`
`TROPIC, NCT0041707915: XRP-6258 with prednisone vs. mitoxantrone with
`prednisone; phase III.
`Sanofi-aventis.
`Ongoing.
`EU (inc UK), USA, Canada and other countries.
`Randomised, open-label.
`n=720; prostate cancer previously treated with docetaxel; documented
`progression of disease; surgical or hormone-induced castration; life expectancy
`> 2 months ECOG PSa 0-2.
`Randomised to mitoxantrone (IV) and prednisone (oral) or XRP-6258 (IV) and
`prednisone (oral), every 3 weeks until disease progression, death, unacceptable
`toxicity, or for a maximum of 10 cycles.
`Maximum 2 years.
`Overall survival.
`
`Progression free survival, overall response rate, prostate-specific antigen (PSA)
`response/ progression, pain response/ progression, overall safety, and
`pharmacokinetics.
`May 2010.
`
`Expected
`reporting date
`
`
`a The ECOG PS (Eastern Cooperative Oncology Group Performance Status) scale assesses a patient’s disease
`progression, living abilities, and determines appropriate treatment and prognosis. The scale runs from 0-5 with:
`0=asymptomatic; 1=symptomatic but completely ambulatory; 2=symptomatic, <50% in bed during the day;
`3=Symptomatic, >50% in bed, but not bedbound; 4=bedbound; 5=death.
`
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`
`(cid:0) Quicker, earlier or more accurate
`diagnosis or identification of
`disease
`
`Services
`(cid:59) Increased use: e.g. length of
` stay, out-patient visits
`
`(cid:0) Decreased use
`
`Costs
`(cid:0) Increased unit cost compared to
`alternative
`(cid:59)New costs: Additional therapeutic
`option
`
`(cid:59)Increased length of survival
`
`(cid:0) Other:
`
`(cid:0) Improved quality of life for patients
`and/or carers
`(cid:0) None identified
`
`(cid:0) Service reorganisation required
`
`(cid:0) Staff or training required
`
`(cid:0) Other:
`
`(cid:0) None identified
`
`(cid:0) Increased costs: more patients
`coming for treatment
`(cid:0) Savings:
`
`(cid:0) Increased costs: capital
`investment needed
`(cid:0) Other:
`
`
`
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`National Horizon Scanning Centre
`News on emerging technologies in healthcare
`
`April 2009
`
`
`Estimated cost and cost impactb
`The cost of cabazitaxel is not yet known. The cost of 6 cycles (18 weeks) of docetaxel at
`a dose of 75mg/m2 IV every 21 days for metastatic HRPC is £5,26216.
`
`Potential or intended impact – speculative
`
`Patients
`(cid:59)Reduced morbidity
`
`
`References
`
`1 National Institute for Health and Clinical Excellence. Docetaxel for the treatment of hormone-refractory
`metastatic prostate cancer. Technology Appraisal TA101. London: NICE; June 2006.
`2 National Institute for Health and Clinical Excellence. Prostate cancer: diagnosis and treatment. Clinical
`guideline CG58. London: NICE; February 2008.
`3 National Institute for Health and Clinical Excellence. Improving outcomes in urological cancers - Manual.
`Cancer service guidance. London: NICE; September 2002.
`4 National Institute for Health and Clinical Excellence. High dose rate brachytherapy for prostate cancer.
` Interventional procedure guidance IPG174. London: NICE; May 2006.
`5 National Institute for Health and Clinical Excellence. Cryotherapy as a primary treatment for prostate cancer.
` Interventional procedure guidance IPG145. London: NICE; November 2005.
`6 National Institute for Health and Clinical Excellence. Low dose rate brachytherapy for localised prostate
` Cancer. Interventional procedure guidance IPG145. London: NICE; November 2005.
`7 National Institute for Health and Clinical Excellence. Cryotherapy for recurrent prostate cancer. Interventional
` procedure guidance IPG119. London: NICE; May 2005.
`8 National Institute for Health and Clinical Excellence. High-intensity focused ultrasound for prostate cancer.
` Interventional Procedure Guidance IPG118. London: NICE; May 2005.
`9 Department of Health Service guideline. Advice on the development of low dose rate (permanent seed implant)
` brachytherapy services for localised prostate cancer in England. November 2006.
`10 The Royal College of Pathologists. Service guidance. Dataset for tumours of the urinary collecting system
` (Renal pelvis, ureter, bladder and urethra). January 2007.
`11 European Association on Prostate Cancer. Guidelines on prostate cancer. March 2007
`12 Cancer Research UK. UK prostate cancer incidence statistics 2009.
` http://info.cancerresearchuk.org/cancerstats/types/prostate/incidence/ Accessed 17 March 2009.
`13 Cancer Research UK. UK prostate cancer mortality statistics 2009.
` http://info.cancerresearchuk.org/cancerstats/types/prostate/mortality/ Accessed 17 March 2009.
`14 Dowling AJ, Tannock IF. Systemic treatment for prostate cancer. Cancer Treat Rev. 1998; 24:283-301.
`15 ClinicalTrials.gov. XRP6258 plus prednisone compared to mitoxantrone plus prednisone in hormone
` refractory metastatic prostate cancer (TROPIC).
` http://www.clinicaltrials.gov/ct2/show/NCT00417079?term=XRP-6258&rank=1#locn Accessed 08 April
`
`b Costings based on an average surface area 1.75m2.
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`News on emerging technologies in healthcare
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`April 2009
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` 2009.
`16 National Institute for Health and Clinical Excellence. Prostate cancer (hormone-refractory) - docetaxel:
` analysis of cost impact London: NICE; September 2006.
` http://www.nice.org.uk/guidance/index.jsp?action=download&o=33354 Accessed 08April 2009.
`
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`
`
`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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