Everolimus may Be Effective Second-line Option After Failure of First-line Tx in Renal-cell Ca

May 31, 2008

Everolimus, an experimental oral agent that targets the mTOR protein, may represent an effective second-line option for patients with metastatic renal-cell carcinoma whose disease has progressed despite treatment with a tyrosine kinase inhibitor.

Everolimus, an experimental oral agent that targets the mTOR protein, may represent an effective second-line option for patients with metastatic renal-cell carcinoma whose disease has progressed despite treatment with a tyrosine kinase inhibitor.

In a Phase 3 study, everolimus doubled progression-free survival compared with placebo, said Robert J. Motzer, MD, the study's lead investigator. The favorable effect of everolimus was so pronounced that the study was stopped following a planned interim analysis after which 60% of the planned number of events had accrued.

Historically, metastatic renal-cell carcinoma has been one of the most difficult cancers to treat. An effective treatment option after the disease has progressed - despite treatment with targeted agents such as sorafenib and sunitinib - is an unmet clinical need, said Dr. Motzer, attending physician, Memorial Sloane-Kettering Cancer Center, New York City. "It is an unmet clinical need that has now been filled," he said. "Everolimus should be standard of care in this setting."

The study included 410 patients with metastatic renal-cell carcinoma with a clear cell component. All patients had stopped responding to either sorafenib or sunitinib within the previous 6 months. "This was a heavily pretreated group," he said. Patients had received up to three therapies previously.

After 6 months, the median progression-free survival was 4 months in patients assigned to everolimus vs. 1.9 months in those assigned to placebo, a hazard ratio of 0.30 (p < 0.0001). Everolimus was significantly superior to placebo in all three prognostic groups (favorable, intermediate, poor).

The most common adverse events in the everolimus group were stomatitis (incidence of 40% vs. 8% with placebo), anemia (28% vs. 15%), and weakness (28% vs. 20%). The incidence of severe (grade 3 or 4) toxicity was 3% or less for each side effect.

Quality-of-life measures were not significantly different between patients randomized to everolimus or placebo.