Patients with kidney cancer could see their treatment options significantly improved with new drugs in late-stage testing reporting gains in survival - over and above those achieved with standard therapy - in clinical trials reported at the American Society of Clinical Oncology meeting.
Until very recently, kidney cancer had seen little in the way of new treatments over the last 20 years, according to Dean Bajorin of Memorial Sloan-Kettering Cancer Center, who said at ASCO that there are now “several promising therapies that are significantly improving survival and response rates” in these patients, who typically only have a 15% survival rate at five years.
ASCO provided an opportunity for oncologists to take a close look at new data that compared Pfizer’s Sutent (sunitinib), approved in January as a second-line treatment on the back of data showing a response rate with the drug of 26% to 37%, to standard first-rank therapy with interferon alfa.
The 750-patient study showed that Sutent nearly doubled progression-free survival – from 25 weeks for interferon to more than 47 weeks with Pfizer’s drug – while response rates were 25% and 5%, respectively. Sutent is delivered orally on an outpatient basis, while interferon alpha is given by injection.
“As a result of this trial, we believe sunitinib will become the new standard of care for advanced renal cell cancer,” said the study’s lead author, Robert Motzer of Memorial Sloan-Kettering Cancer Center, “There were some side effects, including fatigue and reduced blood counts, but because of the overwhelming superiority and efficacy of this drug, and the fact that the side effects were very well tolerated, the benefits clearly outweigh the costs.”
In kidney cancer Sutent will go head-to-head with another new product, Bayer and Onyx' Nexavar (sorafenib tosylate), which was cleared by the FDA late last year. The latter product is also delivered by mouth and both have been tipped as billion dollar sellers by analysts.
Meanwhile, Wyeth has also staked a claim to the kidney cancer sector with temsirolimus, presenting data at ASCO which showed that it too was able to improve survival compared to interferon alfa therapy.
The Phase III study involved 626 patients whose kidney cancer was so advanced and pre-treated that they had a very poor prognosis. They were randomised to either temsirolimus, interferon alpha or combination treatment with the two drugs (using a lower dose of Wyeth’s drug), all administered by injection.
Temsirolimus-reated patients lived for a median of 10.9 months, compared to 7.3 months with interferon alone and 8.4 months for the combination group, while progression-free survival was 3.7 moths, 1.9 months and 3.7 months, respectively.
Presenting the data, Gary Hudes of Fox Chase Cancer Center said the results were significant because temsirolimus is the first of the new-generation of kidney cancer drugs to show an overall survival advantage.
Temirolimus is an inhibitor of mTOR, a signalling protein that regulates cell growth and angiogenesis and is thought to be central to the development of renal cell carcinoma, a common type of kidney cancer. Side effects attributed to the drug included rashes and increased blood glucose, but these were not severe and easily controlled, according to Hudes.
A Wyeth spokesman said the firm plans to file for approval of temsirolimus by the end of the year.
Another drug vying for a role in kidney cancer treatment is GlaxoSmithKline’s Tykerb (lapatinib ditosylate), an orally-active agent which caused a buzz at ASCO with new data in breast cancer patients.
Alain Ravaud of the University of Bordeaux in France presented the results of a Phase III study which gave an indication that Tykerb was able to improve survival in advanced-stage renal cancer patients, although failed to show a statistically-significant advantage for GSK’s drug.
The study compared Tykerb with hormonal therapy (tamoxifen or megestrol acetate) in 416 patients with advanced kidney cancer, and found no difference in overall survival and time to progression between the groups.
However, a prospectively-defined subgroup analysis in patients whose tumours had a high level of epidermal growth factor receptor (EGFR) expression, one of the molecular targets of the drug, found that Tykerb was associated with higher overall survival than hormonal therapy (46 weeks versus 38 weeks), which was a significant result. Time to progression was also improved in this group to 15 weeks from 10 weeks with hormonal therapy.
Ravaud said further studies of Tykerb in kidney cancer are needed, particularly in combination with other drugs and in earlier-stage patients.