Interim results from a Phase III study suggest Wyeth's temsirolimus (CCI-779 or TEMSR) should be standard first-line therapy for advanced kidney cancer, Fox Chase Cancer Center's Gary Hudes said June 4 at the American Society of Clinical Oncology's annual meeting in Atlanta.

"Temsirolimus can be considered standard first-line therapy for patients with metastatic renal cell carcinoma and poor risk features," Hudes said, noting that it is the first new agent to show a statistically significant survival advantage in metastatic renal cell carcinoma.

The three arm study compared temsirolimus as a single agent, temsirolimus in combination with interferon and interferon alone. Overall survival for the three arms was 10.9 months, 8.4 months and 7.3 months, respectively. At the time of the interim analysis, there were 442 deaths in the 626-patient study.

"Compared with interferon alone, treatment with single agent temsirolimus resulted in a 49% improvement in median overall survival and a reduced hazard ratio for death of 0.73," Hudes noted.

Temsirolimus/interferon combination was associated with only a 15% increase in median overall survival and a non-significant reduction in the hazard ratio for death relative to interferon.

The most significant adverse events reported in the interferon, temsirolimus and temsirolimus/interferon combination arms were asthenia (27%, 12% and 30%, respectively), anemia (24%, 21% and 39%) and dyspnea (8%, 9% and 11%).

The proportion of patients experiencing Grade III/IV adverse events was significantly lower in the single agent temsirolimus arm (69%) compared to the interferon (85%) and combination therapy arms (87%).

Hudes said that, based on the results, study of temsirolimus in broader kidney cancer populations is warranted. Temsirolimus is an inhibitor of mTOR (mammalian target of rapamycin), a signaling protein that regulates cell growth and angiogenesis.

"Efficacy of temsirolimus in patients with poor risk features suggest the potential benefit of this agent in broader renal carcinoma populations," Hudes said.

While the temsirolimus/interferon combination regimen was less effective than temsirolimus monotherapy in the trial, Hudes said further study of combination regimens is warranted.

"Temsirolimus can serve as the foundation for the development of rational combination therapies [to] further improve outcomes for patients with metastatic renal cell carcinoma based on mTOR inhibition and addition of agents that target the vascular endothelial growth factor receptor," he said.

Wyeth intends to file an NDA for the renal cell carcinoma indication in the fourth quarter of 2006. FDA granted orphan drug designation to temsirolimus for the treatment of advanced RCC and awarded the claim fast track status.

Were temsirolimus to be approved for RCC, it would be entering an increasingly crowded kidney cancer market. Bayer/Onyx' Nexavar and Pfizer's Sutent recently received approval for kidney cancer claims (¹ Also see "Nexavar “Very Competitive” With Pfizer’s Sutent, Bayer Says" - Pink Sheet, 2 May, 2006.).

Wyeth also conducted a clinical trial of temsirolimus in combination with Novartis' Femara (letrozole) for the treatment of advanced metastatic breast cancer. However, the trial was halted due to a failure to demonstrate increased efficacy over letrozole alone (² Also see "Wyeth Ends Temsirolimus Breast Cancer Trial" - Pink Sheet, 16 March, 2006.).

The company is also studying the agent in treatment of mantle cell lymphoma.

-Turna Ray

Wyeth CCI-779 Survival Benefit Over Interferon In Kidney Cancer May Warrant First-Line Use

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