Temsirolimus Wins FDA Okay to Prolong Survival in Advanced Kidney Cancer

PHILADELPHIA, May 30 -- The drug temsirolimus (Torisel) prolongs survival in patients with metastatic renal cell carcinoma, researchers here reported today.

And in a rare confluence of research results and regulatory action, on the same day that the pivotal randomized trial was published in the New England Journal of Medicine the drug was approved by the FDA for the indication.

For patients getting the drug, median survival was 3.6 months longer than for those getting standard treatment with interferon alfa, Gary Hudes, M.D., of the Fox Chase Cancer Center, and colleagues in the Global ARCC Trial, reported in the May 31 issue of the NEJM.

A third arm of the industry-sponsored study, combining temsirolimus and interferon alfa, did not show any survival benefit over interferon alfa alone, Dr. Hudes and colleagues found.

"This is the first study to show that a new drug can improve overall survival for patients with metastatic renal cell cancer," Dr. Hudes said.

Early last year, sutinib (Sutent) was approved to treat metastatic renal cell carcinoma, but the studies involving that drug showed improvement in progression-free survival, rather than overall survival. (Sutent and Nexavar Put Brakes on Renal-Cell Carcinoma)

Similarly, sorafenib (Nexavar) was approved in December 2005 on the basis of a delay in disease progression in renal cell carcinoma.

While the survival improvement with temsirolimus therapy is "modest," Dr. Hudes said, patients in the study had very advanced tumors.

"It would be reasonable to hypothesize that temsirolimus could provide greater benefit to patients with less extensive metastatic disease," Dr. Hudes said.

The current study was stopped at the second interim analysis, the researchers said, when 446 of the 626 patients had died and there was significant evidence (at P<0.0135) that the drug was providing a benefit.

In the study, patients were randomized to 25 mg of temsirolimus intravenously once a week; to interferon alfa, at a dose escalating from three million to 18 million units, subcutaneously three times a week; or to a combination of 15 mg of temsirolimus weekly and six million units of interferon alfa three times a week.

The study found:

• Median survival for patients getting temsirolimus was 10.9 months, compared with 7.3 months for interferon alfa and 8.4 months for the combination.
• For temsirolimus patients, the hazard ratio for death, compared to interferon alfa, was 0.73 (with a 95% confidence interval from 0.58 to 0.92), which was significant at P=0.008.
• Overall survival for patients in the combination group did not differ significantly from those getting interferon alfa.

Dr. Hudes and colleagues said the lack of efficacy in the combination group may have been a result of the lower dose of temsirolimus.

The study also showed a significantly longer period of progression-free survival (P<0.001) for patients getting temsirolimus, compared with those on interferon alfa, the researchers said.

Temsirolimus was better tolerated than interferon-alfa, with 67% of patients in the temsirolimus group having Grade 3 or 4 adverse events, compared with 78% of interferon patients and 87% of patients in the combination group. Both differences were significant at P=0.02.