Sutent is first agent to extend survival in metastatic renal cancer by over 2 years

Overall survival data from a randomised double blind study comparing first-line sunitinib (Sutent) with the previous standard therapy in metastatic renal cell cancer (mRCC), interferon (IFN) alpha, show sunitinib extends median survival to almost two and a half years. This finding breaks new ground and more than doubles the survival time typically observed with IFN alpha treatment, say experts. Sunitininb, a multi-targeted tyrosine kinase inhibitor (TKI) works on several targets including the vascular endothelial growth factor (VEGF) receptor which promotes the blood supply of tumours, and platelet derived growth factor (PDGF) which is implicated in tumour progression. Dosages used in the study were: sunitinib 50mg orally once daily in six-weekly cycles, four weeks on, two-weeks off; IFN alpha dosage was 9 MU administered subcutaneously three times per week.

Data from the landmark phase III study of 750 patients were presented at ASCO by Dr Robert Figlin of City of Hope Hospital, Duarte, California (1). They confirm earlier promise shown in previously published data from the same study regarding progression-free survival (PFS) which found sunitinib-treated patients experienced an 11-month delay before their cancer worsened – more than double the time observed in IFN-alpha-treated patients (2). The latest analysis on overall survival shows patients who remained on their initial therapies from randomisation, and who did not receive any other treatment before, during or after their participation in the study, had a median survival of 28 months if they received sunitinib and 14 months if they were treated with IFN alpha (p=0.0033). Most patients in the study however crossed over to other treatments when their disease progressed. Overall those randomised initially to sunitinib had a median survival of 26.4 months compared to 21.8 months for those randomised initially to IFN alpha giving a hazard ratio of 0.82 (p,0.05).

The study recruited patients between August 2004 and October 2005. Patients were included if they had histologically confirmed renal cell cancer, no prior systemic treatment, an ECOG performance status of 0 or 1, and measurable disease, Dr Figlin explained. Around 90 per cent of each treatment group had undergone prior nephrectomy and approximately 80 per cent in each group had disease involvement at more than two metastatic sites. The median treatment duration was 11 months for sunitinib and 4 months for IFN alpha. The commonest reason for stopping treatment in each treatment group was disease progression (60 per cent for sunitinib and 65 per cent for IFN alpha). Updated efficacy data show the median PFS was 11 months for sunitinib and 5 months for IFN alpha and objective response rates were 39 and 8 per cent respectively according to independent reviewers, and 47 and 12 per cent respectively according to investigators (p<0.000001). The objective response rates were 31 and 6 per cent (p<0.001) at the time of the first analysis. Earlier results led to sunitinib’s approval in January 2007 in Europe for first-line use in mRCC and it is now recommended as first-line therapy in European Association of Urology (EAU) clinical guidelines.

Discussing the data. Dr Figlin said they confirm sunitinib’s place as the reference standard for first-line therapy for advanced renal cancer. Dr Brian Rini of The Cleveland Clinic, Ohio who acted as discussant following Dr Figlin’s presentation said: “There is no question that patients treated with sunitinib are living longer. Anyone who looks after a substantial number of kidney cancer patients knows more people are coming back for return visits than used to be the case. Survival after sunitinib therapy is much higher than with anything we’ve seen in kidney cancer before by a long shot.”

Co-investigator Sylvie Negrier, Professor of Medical Oncology at University of Lyon agreed. “Sutent is able to shrink tumours well and that really augments survival to a greater degree than hoped,” she noted. Survival prospects for kidney cancer patients are likely to get even better, she believes. “There is still progress to be made. I’m confident that over the next few years the compounds we are using and the new ones we are developing will help us reach our goal of extending life further for kidney cancer patients.” New treatments in development such as Pfizer’s axitinib and Novartis’ everolimus are proving very effective in patients who develop resistance to sunitinib therapy, she noted. Research combining different treatments and identifying the right sequence of therapies will identify the way to optimise treatment outcomes.

Renal cancer represents 2 to 3 per cent of all cancers, and occurs most commonly in developed countries. Each year around 30,000 patients are diagnosed with kidney cancer in the European Union and half that number die from the disease. Five-year survival in Europe is now 57 per cent and is increasing, partly because of better treatments and partly because of improved diagnostic techniques allowing renal cancers to be diagnosed at an earlier and more treatable stage. The development of TKIs is revolutionising the management of renal cancer but their high cost is a world-wide concern and is driving research to predict where treatments have greatest efficacy. Drugs available already for metastatic renal cancer include sunitiniib for first-line treatment, sorafenib for second-line therapy and temsirolimus for poor-risk patients. Other multi-targeted TKIs and other agents in development that have demonstrated activity include lapatinib, axitinib, pazopanib, VEGF Trap and lenalidomide. A combination of the anti-angiogenesis agent bevacizumab and IFN alpha is expected to be approved in 2008 for use in renal cancer. The combination is being investigated in the AVOREN study. Overall survival data from this are expected in the second half of 2008.

1. 1Figlin RA et al. Abstract 5024. JCO 2008; 26 (supplement):256S
2. Motzer RJ et al. NEJM 2007; 356:115-124.