The randomized, phase 3 EVEREST trial analyzed the effectiveness of everolimus, a mammalian target of rapamycin inhibitor, in patients with renal cell carcinoma (RCC) who have undergone full surgical resection. The results were published in The Lancet.
Patients with RCC who undergo resection are at a higher risk of relapse, and therefore additional treatment options are needed to determine if the risk of recurrence can be improved.
The double-blind trial enrolled 1545 patients with RCC who had undergone full surgical resection and had an intermediately high or very high risk of recurrence from 398 academic and community centers across the United States. Each patient underwent nephrectomy and was then randomly assigned to receive either everolimus 10 mg orally daily or placebo for 54 weeks. The study’s primary end point was recurrence-free survival (RFS).
After analyzing patient eligibility, 755 patients were assigned to receive everolimus and 744 were assigned to placebo. The median follow-up was 76 months (interquartile range [IQR], 61-92 months). RFS was longer in patients who received everolimus treatment versus placebo (5-year RFS, 67%; 95% CI, 63-70 vs 63%; 95% CI, 60-67; stratified log-rank P=.050; stratified hazard ratio [HR], 0.85; 95% CI, 0.72-1.00; P=.051). However, it did not meet the prespecified P value of .044 for statistical significance.
RFS was also longer after everolimus administration versus placebo in the very-high-risk group (HR, 0.79; 95% CI, 0.65-0.97; P=.022) but not in the intermediately high-risk group (HR, 0.99; 95% CI, 0.73-1.35; P=.96). Grade 3 or higher adverse events occurred in 46% of patients who received everolimus and 11% of patients who received placebo.
The use of postoperative everolimus did not improve RFS compared with placebo in patients with RCC at high risk of recurrence after nephrectomy. The results of this study do not support the use of everolimus for RCC after surgery.