Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.
On March 30, 2009, the U. S. Food and Drug Administration (FDA) approved everolimus tablets (AFINITOR ®, made by 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 randomly selected (2:1 ratio) 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 percent of patients had died by the time of data cut-off. The objective response rates were 2 percent and 0 percent for everolimus and placebo, respectively. After documented radiological progression, patients receiving placebo could receive everolimus.
The most common adverse reactions (incidence ≥30 percent) were stomatitis, infections, asthenia, fatigue, cough, and diarrhea. The most common grade 3/4 adverse reactions (incidence ≥ 3 percent) were infections, dyspnea, fatigue, stomatitis, dehydration, pneumonitis, abdominal pain, and asthenia. The most common laboratory abnormalities were anemia, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, lymphopenia, and increased creatinine (incidence ≥50 percent). The most common grade 3/4 laboratory abnormalities (incidence ≥3 percent) were phopenia, hyperglycemia, anemia, hypophosphatemia, and hypercholesterolemia. Deaths due to acute respiratory failure (0.7 percent), infection (0.7 percent) and acute renal failure (0.4 percent) occurred on the everolimus arm but not on the placebo arm.
This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products, or Patricia Keegan, M.D., director of the FDA's Division of Clinical Trials Design and Analysis.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Understanding the Approval Process for New Cancer Treatments.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.
For further information related to oncology drug approvals, regulatory information and other oncology resources, please refer to the FDA's
Oncology Tools Web site.
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