New drugs increase progression-free survival in advanced RCC patients

Two new drugs for advanced renal cell carcinoma effectively increase progression-free survival in patients with the disease, according to separate studies published last week in the New England Journal of Medicine (2007; 356:125-34; and 115-24).

Sorafenib (Nexavar) appeared to double median progression-free survival in patients with advanced renal cell carcinoma, according to findings from the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET).

More than 900 patients with advanced RCC were randomized one-to-one to receive either oral sorafenib, 400 mg, or placebo twice a day in the multi-national, placebo-controlled phase III study. Progression-free survival doubled to a median of 5.5 months in patients receiving sorafenib compared with 2.8 months in patients receiving placebo (p<.001). This represented a 56% reduction in the risk of progression (hazard ratio .44; 95% CI, 0.35 to 0.55) for patients on sorafenib versus placebo.

All patient subgroups examined benefited regardless of performance status or risk group, including patients who had not received conventional treatment with biologics, such as interleukin-2 (Proleukin) or interferon-alpha (Intron A).

"This landmark study demonstrated the efficacy, tolerability, and clinical benefit of Nexavar, which has rapidly become a valuable weapon against this devastating disease," said co-principal investigator Ronald Bukowski, MD, of The Cleveland Clinic Taussig Cancer Center.

In a second randomized, phase III trial, sunitinib malate (Sutent) was more effective than the conventional treatment given as an initial therapy in patients with advanced kidney cancer.

The multicenter study, led by Robert Motzer, MD, of Memorial Sloan-Kettering Cancer Center, New York, included 750 patients over the age of 18 years who were diagnosed with advanced kidney cancer and were previously untreated for the disease. Half were treated with a 6-week cycle of sunitinib, and half were treated with a 6-week cycle of interferon-alpha. The median progression-free survival for treatment with sunitinib was 11 months, compared with 5 months following treatment with interferon-alpha.

In addition, 31% of the patients in the sunitinib arm of the study experienced substantial tumor shrinkage compared with 6% of the patients receiving the standard treatment.

Dr. Motzer and his co-authors concluded that sunitinib is a new "reference standard of care" for first-line treatment of advanced kidney cancer.

"These studies are a major step forward in our struggle against kidney cancer," said James Brugarolas, MD, PhD, who authored an editorial about the two studies (N Engl J Med 2007; 356:185-7). "Both sunitinib and sorafenib have clear anti-tumor activity, and while increased anti-tumor activity might reasonably be expected to increase life expectancy, this might not be the case because of toxicities, which could affect patient survival."