CHICAGO—Everolimus, an experimental targeted therapy, significantly delays progression of metastatic kidney cancer in patients whose disease has worsened despite treatment, according to results of a phase III trial.


“This study has given us a new and clearly useful tool for treating renal cell tumors, and everolimus is an important step forward in terms of disease management and quality of life for patients living with this disease,” said lead researcher Robert Motzer, MD, an attending physician at Memorial Sloan-Kettering Cancer Center in New York.

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Everolimus is administered orally and targets the mTOR protein, which regulates cell division and blood vessel growth in cancer cells. It is being evaluated for the treatment of several other cancers, including lymphoma and neuroendocrine tumors. The drug is approved as an immunosuppressant to prevent rejection of organs after transplantation.


The trial included 410 patients with renal cell carcinoma (RCC) with a clear cell component. All had been treated previously with sunitinib, sorafenib, or both. These drugs target a different receptor commonly found in kidney tumors—vascular endothelial growth factor (VGEF)—but had stopped responding.


Investigators randomly assigned 272 patients to receive everolimus and 138 to receive placebo, plus best supportive care (which can include measures such as palliative radiation therapy). After six months, 26% of patients in the everolimus group had not progressed compared with only 2% in the placebo group.


The difference in median progression-free survival was four months for the patients receiving everolimus compared with 1.9 months for the placebo group. 


The most common adverse effects for patients receiving everolimus were mouth ulcers (36% vs. 7% in the placebo group), anemia (28% vs. 15%) and weakness (28% vs. 20%). The instances of severe (grade 3 or 4) toxicity were 5% or lower for each adverse effect.


“We found the safety was acceptable with everolimus and we also looked at quality of life studies and there was no worsening in quality of life compared to placebo treatment,” Dr. Motzer said.


In February 2008, an independent monitoring committee stopped the phase III trial after interim results were positive and allowed researchers to offer everolimus to the patients receiving placebo.


“For almost 20 years, we made no headway in the management of advanced kidney cancer,” Dr. Motzer said.


“Recently, the identification of several new angiogenesis-targeted agents has provided us with new treatment options and an improved outlook for patients with advanced kidney cancer. Based on the results of this trial, everolimus could become another tool in our armamentarium and, in the future, kidney cancer is likely to be managed as a chronic disease with these types of treatment advances.”

Everolimus is the first agent shown to be effective in RCC patients who have failed previous treatment with sunitinib, sorafenib, or both agents, Dr. Motzer said. Pending FDA approval, everolimus should become standard of care for this patient population, he said.


Study findings were reported here at the American Society of Clinical Oncology annual meeting.