Daily Everolimus For Up to 1 Year After Surgery Improves Recurrence-Free Survival in High-Risk Renal Cell Carcinoma

A study of individuals with high-risk renal cell carcinoma (RCC) found that patients administered everolimus (Afintior, Afinitor Disperz, Zortress; Novartis) daily for up to 1 year after surgery lived longer with recurrence-free survival (RFS), though the results missed the clinical trial’s prespecified level for statistical significance.
RFS improvement was seen primarily in individuals with very high-risk RCC, whereas individuals with intermediate high-risk disease saw no improvements in RFS.

The results of the study were presented at the 2022 American Society of Clinical Oncology Annual Meeting on June 3, 2022.

“This is the only adjuvant study in renal carcinoma of the class of therapies called mTOR inhibitors,” Christopher Ryan, MD, professor of medicine at Oregon Health & Science University, said in a statement. “While there were fewer recurrences in patients who took everolimus, the results fell just shy of statistical significance. Patients at the highest risk of recurrence, those with locally advanced tumors or lymph node involvement, appeared to garner the most benefit from treatment.”

The findings were from the phase 3 EVEREST study (S0931 trial), which was conducted by the SWOG Cancer Research Network, a cancer clinical trials group funded by the National Cancer Institute.

Investigators included individuals who had been diagnosed with intermediate high-risk or very high-risk RCC and had their cancer surgically removed by a partial or radical nephrectomy. They randomized 1545 individuals to receive either 1 year of everolimus daily at the 10 mg strength or the placebo, starting within 12 weeks of their surgery.

Approximately 55% of individuals who were enrolled had very high-risk disease, investigators said in the statement.

Overall, RFS was improved in the everolimus arm with a hazard ratio of 0.85; however, the results narrowly missed the pre-specified significance level of 0.022, investigators reported.

Median RFS has not yet been reached for individuals in either arm, but investigators estimate that the 5-year RFS is 67% for individuals in the everolimus arm and 63% for those who are in the placebo arm.

Individuals with very high-risk disease who took everolimus saw a 21% improvement in RFS, but the RFS remained unchanged for those in the intermediate high-risk group, investigators said.

Adverse events (AEs), such as oral mucositis, which is an inflammation of the lining of the mouth, led many individuals to discontinue the treatment. In the everolimus arm, investigators reported that approximately 37% of individuals stopped treatment because of AEs.

Additionally, investigators found that only 45% of individuals in the everolimus arm completed all 54 weeks of study treatment compared to 69% of those in the placebo arm.

“High discontinuation rates of oral adjuvant therapies are common in cancer,” Ryan said in the statement. “Despite the large number of patients who stopped everolimus early, we still observed favorable results for everolimus, which brings into question the duration of adjuvant therapy that is actually needed.”

Reference

Everolimus after surgery can improve outcomes in those with high-risk kidney cancer. EurekAlert. News release. June 3, 2022. Accessed June 3, 2022. https://www.eurekalert.org/news-releases/954480