medwireNews: Adjuvant everolimus may improve recurrence-free survival (RFS) after nephrectomy in people with treatment-naïve renal cell carcinoma (RCC), particularly those with a very high risk for recurrence, suggest final results from the EVEREST trial.
Christopher Ryan, from Oregon Health & Science University in Portland, USA, presented the phase 3 study data at the 2022 ASCO Annual Meeting in Chicago, Illinois, USA.
He reported that, during a median 6.3 years of follow-up, there were 556 disease recurrences or deaths among the 1499 patients included in the intention-to-treat analysis.
The patients had treatment-naïve, non-metastatic, fully-resected RCC and were at intermediate high risk (pT1 G3–4 N0 to pT3a G1–2 N0; 45%) or very high risk (pT3a G3-4 to pT4 G-any or N+;55%) for recurrence.
Within 12 weeks of radical (90%) or partial (10%) nephrectomy, they were randomly assigned to receive 54 weeks of treatment with the mTOR inhibitor everolimus 10 mg/day (n=755) or placebo (n=744).
Ryan told delegates that following treatment median RFS was not reached in either group, but the 5-year estimated RFS rates were 67% and 63% in the everolimus and placebo groups, respectively.
The hazard ratio (HR) for recurrence or death was 0.85 in favor of everolimus, but Ryan noted that the p value of 0.025 did not meet the prespecified statistical significance level of 0.022.
In subgroup analyses, however, the risk for recurrence or death was significantly lower with everolimus than placebo among the patients in the very high-risk group, at a HR of 0.79. By comparison, there was no significant difference between the two arms in the patients who were at intermediate high risk for recurrence.
In total, 290 patients died during follow-up; the estimated 5-year overall survival (OS) rate was 87% with everolimus and 85% with placebo. There was no significant OS difference between the two arms, which Ryan said was “in line with all other adjuvant trials published thus far.”
He noted that “adverse events were consistent with the safety profile of everolimus, but there was a high discontinuation rate in this adjuvant population.”
Specifically, 47% of people given everolimus discontinued treatment for reasons other than disease progression or death compared with 17% of those given placebo. Dose reduction rates were a corresponding 37% and 7%.
“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,” Ryan remarked.
Grade 3 or 4 adverse events occurred in 46% of patients treated with everolimus and 11% of those given placebo, with oral mucositis (14 vs 0%), hypertriglyceridemia (11 vs 2%), and hyperglycemia (5 vs 0%) the most commonly reported.
Ryan concluded that the “compelling results warrant further investigation into the role of everolimus in the current adjuvant landscape and subsets that may benefit most.”
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