Adjuvant everolimus improves recurrence-free survival (RFS) in patients with fully resected renal cell carcinoma (RCC) who have a very high risk of disease recurrence, a phase 3 trial suggests.
However, everolimus does not appear to improve RFS in patients with intermediate high-risk disease, according to Christopher W. Ryan, MD, of the Oregon Health & Science University in Portland. Dr Ryan presented these results at the 2022 ASCO Annual Meeting.
The data come from the phase 3, double-blind EVEREST trial (ClinicalTrials.gov Identifier: NCT01120249), which included 1545 patients with fully resected, nonmetastatic RCC. Patients were randomly assigned to receive everolimus (775 patients) or placebo (770 patients).
In both arms, 55% of patients had very high-risk disease, and 45% had intermediate high-risk disease. The vast majority of patients (83% in the everolimus arm and 84% in the placebo arm) had clear cell RCC.
The median follow-up was 76 months. In the overall study population, everolimus was associated with a numeric improvement in RFS, but this did not meet the prespecified threshold for statistical significance (hazard ratio [HR], 0.85; 95% CI, 0.72-1.00; P =.025). The estimated 5-year RFS rate was 67% in the everolimus arm and 63% in the placebo arm.
A subgroup analysis showed that the effect of everolimus on RFS was more pronounced in the very high-risk group than in the intermediate high-risk group.
There was a significant improvement in RFS with everolimus in the very high-risk group (HR, 0.79; 95% CI, 0.65-0.97; P =.011). The estimated 5-year RFS was 57% with everolimus and 51% with placebo. The median RFS was not reached in the everolimus arm and was 5.3 years in the placebo arm.
On the other hand, there was no significant difference in RFS between the treatment arms among patients with intermediate high-risk disease (HR, 0.99; 95% CI 0.73-1.35; P =.48). The estimated 5-year RFS rate in the intermediate high-risk group was 80% with everolimus and 78% with placebo.
In the entire cohort, overall survival was similar between the treatment arms (HR, 0.90; 95% CI, 0.71-1.13; P =.178). The estimated 5-year overall survival rate was 87% for everolimus and 85% for placebo.
The median time on treatment was 9.3 months in the everolimus arm and 12.6 months in the placebo arm. The percentage of patients who discontinued treatment for reasons other than progression or death was 47% and 17%, respectively.
With respect to the higher discontinuation rate in the everolimus arm, Dr Ryan told attendees that “despite this early discontinuation rate, the fact that we detected this RFS benefit does bring into question the duration of adjuvant therapy that may be needed.”
Grade 3-4 adverse events occurred in 46% of everolimus-treated patients and 11% of placebo recipients. The most common grade 3-4 adverse events were mucositis (14% vs 0%), hypertriglyceridemia (11% vs 2%), and hyperglycemia (5% vs 0%).
“These compelling results warrant further investigation into the role of everolimus in the current adjuvant landscape and subsets that may benefit most,” Dr Ryan concluded.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Ryan CW, Tangen C, Heath EI, et al. EVEREST: Everolimus for renal cancer ensuing surgical therapy—A phase III study (SWOG S0931, NCT01120249). Presented at ASCO 2022, June 3-7, 2022. Abstract LBA4500.