There are about 86,000 new cases of renal cell carcinoma (RCC), the most common form of kidney cancer, and 45,000 deaths in Europe every year. Standard care for RCC has been interferon (IFN)-alpha or interleukin (IL)-2 since the 1980s. But following the results of clinical trials published in January 2007, showing that newer agents have superior efficacy over cytokine-based therapy, the European Association of Urology (EAU) recommended in March first-line use of the oral targeted tyrosine kinase inhibitor (TKI) sunitinib malate (Sutent) in patients with metastatic RCC (mRCC) of good or intermediate risk. Sorafenib (Nexavar) was recommended for second-line use after cytokine therapy and another small molecule targeted therapy, temsirolimus, was recommended for first-line use in mRCC patients with a poor risk status.
Professor Martin Gore, professor of cancer medicine at the Royal Marsden Hospital in London, said: “The development of these new, targeted agents was a huge step forward for the treatment of renal cell carcinoma. But the story of transforming the treatment of kidney cancer is only just beginning and we are now seeing data that are helping us to understand how we can direct these therapies in terms of which patients are likely to receive the most benefit from which therapies.”
New treatments available
The most recent data on this topic were presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago in June. European Association of Urology (EAU) guidelines issued in March recommended multi-targeted tyrosine kinase inhibitors (TKIs) for the treatment of mRCC. The “Guidelines on Renal Cell Carcinoma” recommended that TKIs should be considered as first- or second-line treatment for mRCC patients. Sunitinib malate (Sutent) should be used as first-line therapy in good- and intermediate-risk patients. Sorafenib (Nexavar) was recommended as a second-line treatment for mRCC. Temsirolimus, a specific inhibitor of mTOR, was also recommended as first-line treatment in poor-risk patients.
Sunitinib malate (Sutent) was approved for the first-line treatment of mRCC in January, following a phase III study.(1) Motzer and colleagues enrolled 750 patients with previously untreated mRCC in a multicentre, randomised phase III trial. Patients received either repeated six-week cycles of sunitinib (at a dose of 50mg given orally once daily for four weeks, followed by two weeks without treatment) or interferon alfa (at a dose of 9MU given subcutaneously three times weekly). The primary endpoint was progression-free survival (PFS).
The median PFS was significantly longer in the sunitinib group (11 months) than in the IFN alfa group (5 months), corresponding to a hazard ratio of 0.42 (95% confidence interval [CI], 0.32 to 0.54; p<0.001).(1) An updated analysis of this trial, presented by Dr Motzer at ASCO, showed that the median PFS in sunitinib-treated patients was now 15 months. Moreover, this new analysis suggested that sunitinib prolonged PFS across all patient risk groups, including those with the poorest prognosis. PFS in three prognostic groups for sunitinib versus placebo, respectively, was as follows: favourable risk (14.5 versus 7.9 months), intermediate risk (10.6 versus 3.8 months) and poor risk (3.7 versus 1.2 months). These new data now suggest that sunitinib may also be a reasonable treatment for poorer prognosis patients as well as patients who have a better outlook, although temsirolimus remains the only agent that has demonstrated an overall survival (OS) benefit in poor prognosis patients.(2) In a multicentre, phase III trial, 626 patients with previously untreated, poor-prognosis mRCC were randomised to receive 25mg of intravenous temsirolimus weekly, three million U of IFN alfa (with an increase to 18 million U) subcutaneously three times weekly, or combination therapy with 15mg of temsirolimus weekly plus six million U of interferon alfa three times weekly. The results showed that patients who received temsirolimus alone had longer OS (hazard ratio for death, 0.73; 95% CI, 0.58