Two more targeted therapies for RCC show significant clinical benefits

April 7, 2007

The launch of two targeted therapies in the past 15 months dramatically changed the landscape for renal cell carcinoma, improving the prospects for patients with this deadliest of urologic cancers. The advances in medical treatment for metastatic RCC are not over, however, as two additional targeted therapies have shown great promise in clinical trials and may soon earn FDA approval.

The launch of two targeted therapies in the past 15 months dramatically changed the landscape for renal cell carcinoma, improving the prospects for patients with this deadliest of urologic cancers. The advances in medical treatment for metastatic RCC are not over, however, as two additional targeted therapies have shown great promise in clinical trials and may soon earn FDA approval.

Speaking at the Urology Congress here yesterday, Robert G. Uzzo, MD, FACS, said a greater understanding of the molecular biology of RCC has led to the development of the new therapies. The stage was set in December 2005 with FDA approval of sorafenib (Nexavar), quickly followed by sunitinib (Sutent). Currently in late-stage development are bevacizumab (Avastin) and temsirolimus (Torisel).

"For many targeted agents, the overall response rates are relatively modest, albeit much better than we ever saw with immunotherapy-10% to 40%," Dr. Uzzo, of the Fox Chase Cancer Center in Philadelphia, said of the two approved drugs. "What I think is unprecedented is the clinical benefit of targeted therapy. Not only do many patients have a partial response, but many of them have a stabilization of their disease."

The two agents still under development are likely to complement sunitinib and sorafenib, he said, and combination therapies will likely play a primary role in treatment.

Bevacizumab is a blocker of the vascular endothelial growth factor (VEGF) protein. In a phase II study, patients receiving high-dose IV bevacizumab showed a statistically significant increase in progression-free survival compared with those receiving interleukin-2.

The drug is not useful as monotherapy in RCC, but likely will have a role in combination with other agents, Dr. Uzzo said. A clinical trial examining the efficacy of bevacizumab in combination with interferon has shown improved progression-free survival in an interim analysis.

Temsirolimus, also an IV agent, blocks another protein known as mTOR, which regulates the growth of tumor cells and blood vessels. Phase III data showed that temsirolimus as a single agent significantly improved overall survival and progression-free survival compared with interferon in poor-risk patients.

"It presents another mechanism of action that perhaps can be used in combination in patients with metastatic kidney cancer," Dr. Uzzo said.

All of the targeted therapies are not without toxicities, including hypertension (in up to 60% of patients receiving bevacizumab), stomatitis, and fatigue (each occurring in up to 40% of patients receiving temsirolimus). Overall, toxicities are "manageable," according to Dr. Uzzo.