The FDA ( Food and Drug Administration ) has approved Everolimus tablets ( Afinitor ) 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-alpha 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 ( hazard ratio, 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 greater than or equal to 30% ) were stomatitis, infections, asthenia, fatigue, cough, and diarrhea. The most common grade 3/4 adverse reactions ( incidence greater than or equal to 3% ) 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 greater than or equal to 50% ). The most common grade 3/4 laboratory abnormalities ( incidence greater than or equal to 3% ) were phopenia, 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. ( Xagena2009 )
Source: National Cancer Institute, 2009