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U.S. Department of Health and Human Services

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everolimus

FDA approves everolimus tablets (AFINITOR, Novartis) for treatment of patients with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib

On March 30, 2009, the U. S. Food and Drug Administration granted approval to everolimus tablets (AFINITOR®, Novartis Pharmaceuticals Corporation) for the treatment of patients with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib.

The efficacy and safety of everolimus were evaluated in an international, multicenter, randomized, double-blind trial comparing everolimus to placebo. All patients received best supportive care. The trial was conducted in patients with metastatic renal cell carcinoma after failure of treatment with sunitinib or sorafenib. Prior therapy with bevacizumab, interleukin-2, or interferon-α was also permitted. Randomization was stratified according to prognostic score and prior anticancer therapy.

A total of 416 patients were randomized (2:1) to receive everolimus (n=277) or placebo (n=139). Demographics were well balanced between the two arms. Progression-free survival (PFS) was the trial’s primary endpoint. The median PFS was 4.9 and 1.9 months in the everolimus and placebo arms, respectively (HR = 0.33, p value < 0.0001). The treatment effect was similar across prognostic scores and prior treatment status. The overall survival results were not mature; 32% of patients had died by the time of data cut-off. The objective response rates were 2% and 0% for everolimus and placebo, respectively. After documented radiological progression, patients receiving placebo could receive everolimus.

The most common adverse reactions (incidence >30%) were stomatitis, infections, asthenia, fatigue, cough, and diarrhea. The most common grade 3/4 adverse reactions (incidence >3%) were infections, dyspnea, fatigue, stomatitis, dehydration, pneumonitis, abdominal pain, and asthenia. Anemia, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, lymphopenia, and increased creatinine were the most common laboratory abnormalities (incidence >50%). The most common grade 3/4 laboratory abnormalities (incidence >3%) were lymphopenia, hyperglycemia, anemia, hypophosphatemia, and hypercholesterolemia. Deaths due to acute respiratory failure (0.7%), infection (0.7%) and acute renal failure (0.4%) occurred on the everolimus arm but not on the placebo arm.

The recommended dose of everolimus for treatment of advanced renal cell carcinoma is 10 mg once daily at the same time either with or without food.

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available in Drugs@FDA