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Medical Devices

First UK Guidelines For Kidney Cancer Recommend Pfizer's Sutent(R) (sunitinib) As A First-line Treatment For Metastatic Renal Cell Carcinoma

Today Sutent® (sunitinib) has received a recommendation as a first-line treatment of choice for metastatic renal cell carcinoma (mRCC) in the first ever independent clinical guidelines published on the systemic treatment of renal cell carcinoma (RCC) for the UK.1 The guidelines, presented today at the British Journal of Hospital Medicine conference on renal cancer, come just seven weeks after the National Institute for Health and Clinical Excellence (NICE) published final guidance recommending the use of sunitinib as a first-line treatment of mRCC.2 The guidelines, authored by five leading renal oncologists and supported by an additional 25 renal oncologists nationwide are published in the British Journal of Hospital of Medicine this month. "It is important that UK RCC oncologists have a set of robust clinical guidelines, regarding the use of breakthrough treatments such as sunitinib, that reflect true clinical practice," commented one of the lead authors Professor John Wagstaff, Professor and Honorary Consultant in Medical Oncology, South Wales Cancer Institute, Swansea and Director of the Wales Cancer Trials Network. He continued "These guidelines along with recently published NICE guidance will ensure that kidney cancer patients across the UK will have access to the most beneficial treatment available to them." Sunitinib is the only oral treatment to show overall survival greater than two years in advanced kidney cancer patients.3 Median overall survival for patients who received sunitinib vs interferonalpha (IFN-í±) was 26.4 months vs. 21.8 months respectively (p=0.051). However, an exploratory analysis of patients who received only one line of treatment (i.e. no subsequent treatments after stopping their sunitinib or IFN-í± therapies) showed that sunitinib almost doubles the time to median overall survival compared to IFN-í± [28.1 months vs 14.1, HR = 0.647 (p=0.0033, log-rank]) 3. This is a reflection of clinical practice in the UK where generally patients are only funded for one line of treatment at most. Until recently, treatment options were limited to IFN-í±, the current NHS funded standard of care.4 It is estimated that more than 7,000 people are diagnosed with kidney cancer in the UK each year and approximately 3,600 people die from the disease.5 Before NICE guidance only a third (33%) of PCTs (primary care trusts) were funding sunitinib to some extent. Since the guidelines were published (25th March 2009) 90% of PCTs have committed to full funding of sunitinib in accordance with NICE guidance, bringing the UK in line with Western Europe where eligible patients with advanced kidney cancer have been routinely prescribed sunitinib for some time.6 Sunitinib, an oral medicine, received marketing authorisation in July 2006 and was approved as a first-line treatment for mRCC in January 2007. It is a novel addition to a new class of "multi-targeted" anti-cancer drugs. It targets the tumour with a dual action approach, by stopping the cancer cells from multiplying and also cutting off the tumour"s blood supply. Sunitnib for the treatment of GIST Sunitinib is also indicated for the treatment of unresectable and/or metastatic malignant gastrointestinal stromal tumour (GIST) after failure of imatinib mesylate. Updated results from the sunitinib phase III study in GIST patients who failed on imatinib therapy showed a greater than fourfold increase in time to progression (TTP) in sunitinib patients (27.3 weeks) compared with those treated with placebo (6.4 weeks). Sunitinib treatment yielded significant improvement in survival rates versus placebo at three and six months although with 88% of patients in the placebo arm ultimately crossing over to sunitinib, the overall survival was similar between groups.7 Sunitinib is licensed for the first and second line treatment of mRCC and the second-line treatment of GIST. Sunitinib is currently undergoing an appraisal by NICE for the second-line treatment of GIST. In 2007, Pfizer cut the price of sunitinib by five per cent and committed to providing one cycle/course of the treatment free of charge to every eligible patient in the UK, in an effort to increase patient access. This move amounts to an average saving of between 19 per cent and 29 per cent per patient for the cost of treatment, depending upon the type and stage of their tumour. One six-week cycle of sunitinib costs á£3,138.80 (28 tablets of 50mg) in the UK. The average annual cost in the UK for a patient taking sunitinib is á£24,168 (this price includes one free treatment cycle). About Sunitinib Sunitinib is a novel, oral, multi-targeted cancer therapy that selectively targets multiple receptor tyrosine kinases (RTKs) involved in tumour growth, angiogenesis and the progression of cancer. By inhibiting these RTKs, sunitinib targets multiple signaling pathways resulting in a dual action anti-proliferative and antiangiogenic effect, which may lead to tumour regression and disease stabilisation. The recommended starting dose for sunitinib is 50mg once daily for four weeks followed by two weeks off. The dose can be modified in 12.5mg increments not to exceed 75mg or decrease below 25mg. Sunitinib is available in 12.5 mg, 25mg, and 50mg capsules. Please refer to the Summary of Product Characteristics (SPC) for additional dosing recommendations regarding co-administration with cytochrome 3A4 inducers or inhibitors. Adverse events (AEs) were generally mild to moderate. Most adverse events were reversible, and generally did not result in discontinuation. In clinical trials, the most common treatment related adverse events (>20%) included fatigue; gastrointestinal disorders, such as diarrhoea, nausea, stomatitis, dyspepsia, and vomiting; skin discolouration; dysgeusia (loss of taste); and anorexia. Fatigue, hypertension and neutropenia were the most common grade 3 treatment related adverse events. Increased lipase (2%) was the most common grade 4 treatment related adverse event. Hepatitis and hepatic failure occurred in About Pfizer Pfizer Inc, the world"s largest research-based pharmaceutical company, discovers, develops, manufactures and markets prescription medicines in 11 therapeutic areas including oncology, cardiovascular, pain, neuroscience and infectious diseases, including HIV/AIDS. Pfizer is also the world"s largest animal health company. Pfizer Inc employs approximately 90,000 colleagues worldwide, all of whom are devoted to working for a healthier world. Pfizer conducts more biomedical research than any other organisation, and has 12,000 professionals working in six major R&D sites worldwide, including Sandwich in Kent. Pfizer"s annual UK R&D investment is more than á£550 million - more than á£10 million a week. In the UK, Pfizer has its European R&D headquarters at Sandwich and its UK business headquarters in Surrey, and is the major supplier of medicines to the NHS. About Pfizer Oncology Pfizer Oncology is committed to advancing the scientific understanding of cancer and to bringing new medicines to address unmet medical needs in cancer patients. Oncology is a research priority for Pfizer, with over 12 percent of the company"s research and development investment devoted to discovering and developing innovative therapies for treating breast, colorectal and other cancers. References 1. BJHM reference 2. The National Institute for Health and Clinical Excellence http://www.nice.org.uk Accessed March 2009 3. Figlin RA et al. Overall survival with Sunitinib versus Interferon-alfa (IFN-) as First-line Treatment of Metastatic Renal Cell Carcinoma (mRCC), Abstract 5024 presented at ASCO 2008 4. Motzer RJ et al. Activity of SU11248, a multitargeted inhibitor or vascular endothelial growth factor receptor and platelet-derived growth factor receptor in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology Jan 06 24:16-24 5. Cancer Research UK. Available here. Accessed 14 May 2008. 6. Ljungberg B, Hanbury D.C, Kuczyk A.S, et al. Guidelines on Renal Cell Carcinoma. European Association of Urology 2007 (Page 22) 7. Demitri GD et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Published online 10 October, 2006. SUR09/057 Pfizer


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