Taking everolimus after surgery may improve outcomes in patients with high-risk renal cell carcinoma

In a study of patients with high-risk renal cell carcinoma, those who took the drug everolimus daily for up to a year after surgery lived longer without their disease recurring (recurrence-free survival, or RFS ) than those who did not take everolimus, although the results narrowly missed the predefined clinical trial level for statistical significance. Improvement was seen primarily in patients with very high-risk disease, while patients with intermediate-risk disease saw no improvement in RFS.

The results come from the Phase III S0931 trial, also known as the EVEREST study, conducted by the SWOG Cancer Research Network, a cancer clinical trials group funded by the National Cancer Institute (NCI). They will be presented at the 2022 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago on June 3.

The study was led by Christopher W. Ryan, MD, a SWOG researcher who is a professor of medicine at Oregon Health & Science University.

This is the only adjuvant study in renal cell carcinoma of the class of therapies called mTOR inhibitors. Although there were fewer recurrences in patients taking everolimus, the results were just below statistical significance. Patients at the highest risk of recurrence – those with locally advanced tumors or lymph node involvement – seemed to benefit most from treatment.”

Christopher W. Ryan, MD, a SWOG Investigator

The EVEREST trial enrolled patients who had been diagnosed with high-intermediate or very high-risk renal cell carcinoma and whose cancer had been surgically removed by partial or radical nephrectomy. The study randomized 1,545 of these patients to one year of everolimus (one 10 mg pill daily) or placebo, starting within 12 weeks of their surgery.

Overall, in all patients, RFS was improved in the everolimus arm: a relative risk (HR) of 0.85, with a 95% confidence interval (CI) of 0.72-1.00 with a P value of 0.025. These results, however, narrowly missed the pre-specified significance level of 0.022.

The median RFS has not yet been reached for patients in both arms, but estimates for five-year RFS are 67% for patients in the everolimus arm and 63% for those in the placebo arm.

EVEREST patients with very high-risk disease (55% of enrollees) who took everolimus saw a 21% improvement in RFS (HR: 0.79; 95% CI 0.65 -0.97), while the RFS was essentially unchanged for those in the high-risk middle phase. risk group (HR: 0.99; 95% CI: 0.73-1.35).

Adverse events (side effects) such as oral mucositis (inflammation of the lining of the mouth) have led many patients to discontinue treatment. In the everolimus arm, 37% of patients discontinued treatment due to adverse events they were experiencing. In fact, only 45% of patients in the everolimus arm completed 54 weeks of study treatment, compared to 69% in the placebo arm.

“High dropout rates from oral adjuvant therapies are common in cancer,” Dr. Ryan said. “Despite the large number of patients who stopped everolimus early, we still observed favorable results for everolimus, which calls into question the duration of the adjuvant treatment really necessary.”

Study S0931 is supported by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), led by SWOG, and conducted by the NIH-funded National Clinical Trials Network (NCTN). The Alliance for Clinical Trials in Oncology, cancer research group ECOG-ACRIN and NRG Oncology have also enrolled patients in the trial.

S0931 was funded by the NIH/NCI through grants CA180888, CA180819, CA180820, and CA180821; in part by Novartis Pharmaceuticals Corporation; and in part through a grant from The Hope Foundation through the SWOG Trial Support (STrS) program.


SWOG Cancer Research Network

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