After years of limited treatment options for people with the most common type of kidney cancer, new drugs with the potential to extend lives are coming to market.
In the past six months, the Food and Drug Administration has approved two new drugs, Sutent from Pfizer Inc. (PFE) and Nexavar from Onyx Pharmaceuticals Inc. (ONXX) and Bayer AG (BAY), for the treatment of advanced renal-cell carcinoma, or RCC. The disease accounts for about 90% of all cases of kidney cancer in the U.S., according to the American Cancer Society.
Wyeth (WYE) plans to apply by the end of this year for FDA approval of its experimental RCC treatment, temsirolimus. And Genentech Inc. (DNA) is studying its colorectal-cancer drug Avastin in kidney-cancer patients.
New studies for these and other drugs have made kidney-cancer treatment one of the hottest topics at this year's annual meeting of the American Society of Clinical Oncology, a gathering of about 25,000 cancer specialists in Atlanta. Amid the flurry of data, drug companies and doctors who led the studies have made competing claims about which will become the new standard of care.
Even with the advances, however, the outlook for people with advanced RCC remains relatively grim. None of the drugs cures RCC, and studies so far show that some can extend lives only by months, not years.
Still, researchers say real progress has been made, and they hope more studies of the latest drugs and others in the pipeline will help improve the outlook further.
"This is a watershed moment for kidney cancer research," Robert Figlin, an oncologist from UCLA Medical Center in Los Angeles who helped conduct the Wyeth study, said in an interview here. The newer drugs "allow patients to live a longer, more comfortable and productive life, and our challenge going forward is to convert this benefit into something more durable," he added.
About 32,000 new cases of RCC are diagnosed in the U.S. each year, according to the National Institutes of Health, and some 12,000 die from the disease every year. It's most common in people between 50 and 70 years old. The survival rate is highest if the kidney tumor is found in an early stage and hasn't spread. But in people whose RCC has spread to the lymph nodes or other organs, only about 15% live for more than five years.
One option in most early-stage RCC cases, as well as some late-stage cases, is surgery to remove all or part of a kidney, followed by careful monitoring, Figlin said. For advanced stages, where the disease has spread, two drugs were introduced over the last two decades: interferon and interleukin. But the more common of the two, interferon, has had a relatively low response rate in patients. And interleukin appears to be effective only in a small number of patients, and it is difficult to administer, doctors say.
"It's been considered historically one of the most resistant cancers to treatment," Robert Motzer, a cancer specialist at Memorial-Sloan Kettering Cancer Center in New York and lead author of a new Sutent study, said at a press conference here Sunday.
About 20 years ago, scientists discovered the genetic abnormality linked to kidney cancer, said Figlin of UCLA. That spurred more research to find ways to inhibit the abnormality, which is finally paying off with new drugs.
Both Bayer's Nexavar and Pfizer's Sutent are part of a class of new drugs known as multikinase inhibitors. The oral medications are designed to interfere with the growth of both cancer cells and the blood vessels that feed tumors.
FDA approved Nexavar in December. The agency based its approval on a trial showing Nexavar doubled to six months the time between the start of treatment and tumor growth or death, compared with three months in people taking a placebo, or fake pill. Sutent received FDA approval in kidney cancer in January based on studies showing the drug shrank tumors in people with metastatic kidney cancer whose tumors had progressed following prior therapy. Sutent also was approved to treat gastrointestinal stromal tumors.
Kidney Drugs Still Show Effectiveness In Studies
Newer studies presented at ASCO further confirmed the effectiveness of these drugs, researchers said. In one trial, RCC patients taking Sutent had progression-free survival for an average of 11 months, compared with five months for people taking interferon, researchers said Sunday. Progression-free survival is a measure of the time between the start of treatment and tumor growth or death.
In another trial, RCC patients taking Nexavar lived for 19.3 months, compared with 15.9 months for patients on placebo, according to data presented Monday at ASCO.
Wyeth's temsirolimus has a different mechanism than Sutent and Nexavar. It's designed to inhibit a protein called mTOR, which regulates tumor growth and cell survival.
A study presented at ASCO compared temsirolimus with interferon and a combination of both. Patients who took temsirolimus lived an average of 10.9 months, those on the combination therapy lived an average of 8.4 months, and those taking interferon had average survival of 7.3 months, the study found.
So which drug works best, and potentially has the best sales prospects? It's hard to say because none of the major studies compared the drugs to each other. What's more, the goals, patient populations and control groups differed among studies. Wyeth's temsirolimus study, for instance, had patients with the worst prognoses, while trials of other drugs included more patients with better prognoses. Meanwhile, Nexavar was compared to placebo, while both temsirolimus and Sutent were compared to interferon.
Still, the differences in the study makeups didn't stop some of the researchers from drawing conclusions. Gary Hudes, lead author of the temsirolimus study and a cancer specialist at Fox Chase Cancer Center in Philadelphia, said temsirolimus should be considered as standard therapy for advanced RCC, while Motzer essentially said the same of Sutent.
Bayer and Onyx say Nexavar is the only approved new RCC treatment to show an overall survival benefit, noting that temsirolimus isn't on the market yet and Sutent's data show progression-free survival, not overall survival. But the Nexavar survival improvement wasn't statistically significant.
From a financial perspective, the market opportunity could be big. Bear Stearns analyst John Boris estimates 2010 Sutent sales of $920 million, which would include its use in gastrointestinal stromal tumors and possibly future indications. He sees 2010 temsirolimus sales of $355 million. Friedman Billings Ramsey analyst Jim Reddoch estimated 2010 U.S. Nexavar sales of $307 million.
The drugs have various side effects. Some patients taking Sutent and Nexavar experienced diarrhea and high blood pressure, while some on temsirolimus had weakness and fatigue and high blood sugar levels.
ASCO has featured studies of other drugs in kidney cancer, but their prospects are less clear. GlaxoSmithKline PLC's (GSK) experimental Tykerb, for example, didn't improve overall survival in a study of RCC patients when compared to hormonal therapy. But it did find a survival improvement among a subgroup of patients whose tumors had the highest amounts of a certain protein targeted by Tykerb. Glaxo initially plans to seek FDA approval for Tykerb as a breast-cancer treatment.
Further studies of the newer kidney-cancer treatments are in the works, including some that combine the treatments. It's also possible that some of the drugs might eventually treat earlier-stage kidney cancer.
"More and more you will meet people who go from treatment to treatment to treatment," Hudes said. And instead of seeing survival improvements of several months, such sequential treatment - or combining drugs - might eventually extend lives by years. "That's the hope," he said.
(Jennifer Corbett-Dooren contributed to this article.)