Recurrence-free survival was not improved by adjuvant everolimus therapy in patients with renal cell carcinoma at high risk of recurrence after nephrectomy, according to the results of the EVEREST trial. The authors conclude, “These results do not support the adjuvant use of everolimus for renal cell carcinoma after surgery.”
At 398 U.S. academic and community centers, adults with histologically confirmed renal cell carcinoma who had undergone a full surgical resection and were at intermediate-high or very high risk of recurrence were randomized to oral everolimus 10 mg or placebo once daily for 54 weeks. Based on a primary endpoint of recurrence-free survival, the phase 3 trial showed the following: “Between April 1, 2011, and Sept 15, 2016, a total of 1,545 patients were randomly assigned to receive everolimus (n = 775) or placebo (n = 770), of whom 755 assigned to everolimus and 744 assigned to placebo were eligible for inclusion in the efficacy analysis. With a median follow-up of 76 months (IQR 61–92), recurrence-free survival was longer with everolimus than with placebo (5-year recurrence-free survival 67% [95% CI 63–70] vs 63% [60–67]; stratified log-rank P = 0.050; stratified hazard ratio [HR] 0.85, 95% CI 0.72–1.00; P = 0.051) but did not meet the prespecified P value for statistical significance of 0.044. Recurrence-free survival was longer with everolimus than with placebo in the very-high-risk group (HR 0.79, 95% CI 0.65–0.97; P = 0.022) but not in the intermediate-high-risk group (0.99, 0.73–1.35; P = 0.96). Grade 3 or higher adverse events occurred in 343 (46%) of 740 patients who received everolimus and 79 (11%) of 723 who received placebo.”