Horizon Scanning Technology Briefing. Sutent (Sunitinib) for first-line and adjuvant treatment of renal cell carcinoma

Transcription

1 Horizon Scanning Technology Briefing National Horizon Scanning Centre Sutent (Sunitinib) for first-line and adjuvant treatment of renal cell carcinoma August 2006: Updated October 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.

2 Sutent (Sunitinib) for first-line and adjuvant treatment of renal cell carcinoma Target group First line metastatic renal cell carcinoma (mrcc) o monotherapy o in combination with interferon alfa (INF-a) Adjuvant to tumour resection in locally advanced renal cell carcinoma (LRCC) Second-line Sutent received conditioning marketing approval in July 2006 for the treatment of advanced and/or metastatic renal cell carcinoma after failure of INF-a or interleukin-2 therapy - previously reported by NHSC in January Update October 2006: In October 2006, the EMEA recommended a switch from the conditional marketing authorisation to a full market authorisation for Sutent. It also recommended extending the indication in mrcc to first-line treatment. Technology description Sutent (Sunitinib; SU11248) is an oral multi-targeted tyrosine kinase inhibitor with antitumour and anti-angiogenic activity in development for first-line treatment of metastatic renal cell carcinoma (mrcc, stage IV). It is also in phase III trials as an adjuvant treatment for locally advanced renal cell carcinoma (LRCC). Sutent inhibits the plateletderived growth factor (PDGF), vascular endothelial growth factor (VEGF), KIT and FLT3 receptors on cancer cells, vascular endothelial cells and pericytes. Sutent is administered orally in a six week cycle; 50mg per day for four weeks, followed by a break of two weeks before repeating the cycle until disease progression. Sutent received European approval in July 2006 for unresectable and/or metastatic malignant gastro-intestinal stromal tumours (GIST) after failure of imatinib mesylate due to resistance or intolerance. It is also in phase II trials for neuroendocrine tumours in patients not eligible for surgical curative treatment; metastatic colorectal cancer refractory to 5FU, irinotecan and oxaliplatin; and metastatic breast cancer in patients who have failed anthracycline and taxane regimens and non-small cell lung cancer. Innovation and/or advantages Oral treatment with potentially fewer side effects. Patients can be managed on an outpatient basis, providing a reduction in the need for specialist care. Increased response rates and progression free survival in first-line mrcc compared with INF-a. Developer Pfizer Ltd. Purpose Diagnosis or identification of disease Prevention e.g. immunisation, public health programme Continuous therapy e.g. dialysis, life support Investigation, assessment or staging of known disease Screening programme or tests to identify latent or early disease Patient management and pathways of care Susceptibility testing for identifying risk of disease Individual treatment e.g. drug, device, procedure, radiotherapy Rehabilitation Aug

3 Service delivery changes Other: National Horizon Scanning Centre Place of use Home care e.g. home dialysis Secondary care e.g. general, non-specialist hospital General public e.g. over the counter Community or residential care e.g. district nurses, physio Tertiary care e.g. highly specialist services or hospital Other: Primary care e.g. used by GPs or practice nurses Emergency care e.g. paramedic services, trauma care Stage of development and availability in EU/UK Phase III clinical trials or Pre-registration in EU (drugs) equivalent Licence or CE mark application in Licence or CE mark application in UK/EU likely within 12 months UK/EU likely within 24 months Launch or use in UK/EU likely Established product, but this is a within 24 months new indication in development CE marked, but not yet launched or available in UK Launch or use in UK/EU likely within 12 months Other: Orphan drug status: Orphan drug status in EU Orphan drug status in USA 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: Relevant guidance NICE Urological Cancer Service Guidelines (2002) 1 Clinical need and burden of disease In 2002, there were 5,872 new kidney cancers diagnosed in England and Wales, of which an estimated 85% (4,991 cancers) were renal cell carcinomas (RCC) 2. RCC is more common in men than women and most commonly affects adults aged years. In 2004, there were 3,134 deaths from kidney cancer in England and Wales 2. Five-year survival in men is 45% and 44% in women 2. Approximately 30% of newly diagnosed cases of RCC (1,497 patients per year) present with metastatic disease (stage IV) and would be eligible for first-line therapy 3. Without treatment, these patients have a median survival of only 6-12 months and a two-year survival rate of 10-20% 4. In addition, an estimated 50% of patients (1,620 patients) who have curative resection for earlier stages of RCC will develop recurrent and/or metastatic disease and may also be eligible for therapy 3. Existing comparators and treatments MRCC Radical nephrectomy (surgical removal of the kidney, adrenal glands and neighbouring lymph nodes) performed prior to immunotherapy may improve survival, however few patients are sufficiently fit to undergo major surgery 1. Cytokines interferon-alpha (INF-a, Roferon A) and/or interleukin-2 (IL-2, aldesleukin, Proleukin) - associated with severe morbidity (physical and mental side effects). Aug

4 Sorafenib (Nexavar) Bayer, for the treatment of cytokine-refractory mrcc received a European licence in July 2006 referred to NICE January 2006 for guidance. LRCC Radical or partial nephrectomy. Efficacy and safety Indication Metastatic Metastatic Locally advanced Trial name or code First-line monotherapy vs INF-a 5 (A ) First-line in combination with INF-a 6 (A ) First-line adjuvant vs sorafenib 7 Sponsor National Cancer Institute, Pfizer Pfizer National Cancer Institute Status Abstract (interim Ongoing Ongoing analysis) Location International US US Design - randomised, controlled. Phase III, randomised, open-label, controlled. Phase III, randomised, open-label, controlled. controlled. Participants in trial number, description, trial schedule e.g. placebo or comparator n=750 (375 per treatment arm). Chemo- and immunotherapy-naive patients (90% had prior nephrectomy) Arm 1: Sutent 50mg once daily on days 1-28 Arm 2: INF-a 9MU s.c. on days 1,3,and 5 weekly for 6 weeks. Courses repeat every 42 days n= 499. Two-part trial Part 1: dose finding study for combination use (non randomised). Part 2: Sutent vs sutent in combination with INF-a. Follow-up Day 30, then every 2 28 days 9 years months Primary outcome Progression free survival Pt 1 - safety; tolerability Pt 2 - time to progression markers Secondary Response rate; overall outcomes survival; QoL Key results Expected reporting date Major adverse effects Objective response rate; overall survival; patient reported outcomes; safety; cost-effectiveness. Median progression-free survival Sutent 11 months vs. INF-a 6 months; objective response rate: Sutent 25% vs. INF-a 5%. Interim analysis expected end 2006; final analysis expected mid Recruitment not expected until Oct st interim analysis expected Phase III, randomised, double blind, placebo n= 1,332. Post-partial or radical nephrectomy. Arm 1: Sutent once daily days 1-28 and placebo. Arm 2: Sorafenib twice daily days 1-42 and placebo Arm 3: Double placebo. Cycles every 6 weeks for up to 9 courses Disease free survival, genetic & biochemical Overall survival; safety and tolerability 2011 at earliest Fatigue, diarrhoea, nausea, neutropenia, anaemia and thrombocytopaenia. Discontinuation of treatment occurred in 8% of patients receiving sutent, compared with 13% receiving interferon. Aug

5 Estimated cost and cost impact The maximum cost of Sutent is 3,304 per six-week treatment cycle, giving an annual cost (based on 8 cycles) of 26,432 per patient. These costs would be in addition to INF-a if used in combination. Potential or intended impact speculative No barriers to diffusion are anticipated, other than the potential higher cost compared with current treatments in first-line mrcc, which may be offset by a reduction in the need for specialist care. In locally advanced RCC as observation is the current standard of care post tumour resection, adjuvant treatment would be an additional cost. Patients Reduced morbidity Quicker or more accurate diagnosis Reduced mortality or increased survival Earlier identification of disease Improved quality of life for patients and/or carers Changed pathway of care or outcome Services Increased use e.g. length of stay, Service reorganisation required out-patient visits Decreased use e.g. shorter length of stay, reduced Other: referrals Staff or training required Costs Increased unit cost compared to alternative Increased costs: more patients coming for treatment Savings: oral treatment provided on an outpatient basis versus current in-patient specialist care References Increased costs: capital investment needed 1 NICE guideline on cancer services: Improving outcomes in urological cancers. The manual. September Cancer Research UK, Incidence-UK, CancerStats Monograph. February Porta C, Zimatore M, Imarisio I et al. Gemcitabine and oxaliplatin in the treatment of patients with immunotherapy-resistant advanced renal cell carcinoma: Final results of a single institution phase II study. Cancer. 2004; 100: Campbell SC, Flanigan RC, Clark JI. Nephrectomy in metastatic renal cell carcinoma. Curr Treat Options Oncol. 2003; 4: Motzer RJ, Hutson TE, Tomczak P. Phase III randomised trial of sunitinib maleate (SU11248) versus interferon-alfa as first-line systemic therapy for patients with metastatic renal cell carcinoma. J Clin Oncol ASCO Annual Meeting Proceedings Part I. Vol 24 (18S June 20 Supplement) LBA3 (Abstract). 6 ClinicalTrials.gov. Sunitinib maleate alone and in combination with interferon alfa as first-line therapy for metastatic renal cell carcinoma. Available online at Accessed 13/07/ ClinicalTrials.gov. Sunitinib or Sorafenib in treating patients with kidney cancer that was removed by surgery. Available online at Accessed 13/07/2006. The National Horizon Scanning Centre is funded by the Research and Development Division of the Department of Health, England The National Horizon Scanning Centre, Aug

6 Department of Public Health and Epidemiology University of Birmingham, Edgbaston, Birmingham, B15 2TT, England Tel: +44 (0) Fax +44 (0) Aug