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Renal Cell Carcinoma · Medical · Adjuvant Therapy

EVEREST

After nephrectomy for intermediate-high or very-high-risk RCC, does adjuvant everolimus improve recurrence-free survival?

Population1,545 randomized patients after complete RCC resection; 755 everolimus and 744 placebo were eligible for efficacy analysis.InterventionEverolimus 10 mg daily for 54 weeks.ComparatorPlacebo.Primary endpointRecurrence-free survival.

Absolute Effect

Overall 5-year RFS
67% vs 63% (+4 points)

HR 0.85 (95% CI 0.72–1.00), P=.051; the prespecified significance threshold was not reached.

Very-high-risk subgroup
HR 0.79

RFS benefit was seen in the very-high-risk group, but subgroup findings should not replace the primary analysis.

Toxicity

Grade ≥3 adverse events occurred in 46% with everolimus versus 11% with placebo. Treatment completion was also substantially lower with everolimus.

Clinical interpretation

EVEREST did not meet its prespecified threshold for a positive primary endpoint despite a numerically higher 5-year RFS.

The absolute difference was 4 percentage points at 5 years, while toxicity was considerably higher. The very-high-risk subgroup generated a hypothesis of differential benefit but was not the primary powered comparison.

NNT / NNH

Using the overall 5-year RFS difference gives an approximate NNT of 25, but the P value narrowly missed the prespecified threshold and the estimate should be treated as descriptive rather than as proof of benefit. For grade ≥3 adverse events, the absolute excess was 35 points, giving an approximate NNH of 3; this endpoint is broad but illustrates the treatment burden.

Limitations

The trial included heterogeneous RCC risk groups and non-clear-cell histology. The absolute recurrence rate reflects the selected high-risk population and historical adjuvant landscape.

Primary / authoritative sources

EVEREST primary report — PubMed

Very-high-risk clear-cell secondary analysis — PubMed

Current-practice context · reviewed 14 October 2026

EVEREST did not meet its prespecified primary endpoint for adjuvant everolimus after nephrectomy and had substantial grade ≥3 toxicity and treatment discontinuation. Adjuvant everolimus is not a standard strategy. Current postoperative discussion should instead consider surveillance and the distinct evidence for adjuvant pembrolizumab in eligible high-risk clear-cell RCC, while weighing immune toxicity and patient preferences.

EVEREST primary source ↗ · Current guideline guidance ↗