A secondary analysis from the phase III SWOG S0931 EVEREST trial found patients with clear cell renal cell carcinoma at very high risk of recurrence after nephrectomy who received adjuvant everolimus had a statistically significant improvement in recurrence-free survival compared to patients who received placebo after surgery. The results may inform the design and development of future adjuvant clinical trials in patients with high-risk disease, according to the study authors. The study will be presented by Primo Lara, Jr, MD, and colleagues at the European Society of Medical Oncology (ESMO) Congress 2023 (Abstract 1887P).
Primo Lara, Jr, MD
The trial’s primary results—which were published earlier this year by Ryan et al in The Lancet—found that although recurrence-free survival was longer for patients randomly assigned to receive adjuvant everolimus, the difference narrowly missed meeting the criterion for statistical significance. In this secondary analysis, the researchers reported their findings in a subset of patients with renal cell carcinoma with clear cell histology who were considered to have a very high risk of disease recurrence.
Methodology
The researchers identified patients with renal cell carcinoma with any clear cell component at very high risk for disease recurrence postnephrectomy. They defined high-risk as patients with pT3a (grade 3-4), pT3b-c (any grade), T4 (any grade), or node-positive disease. A Cox regression model stratified by performance status was used to evaluate recurrence-free survival and overall survival.
Results
Of the nearly 1,500 patients enrolled in the study, 717 had both clear cell and very high-risk disease; 699 patients were eligible for this analysis (348 in the everolimus arm and 351 in the placebo arm). Only 163 of 348 (47%) of the patients receiving everolimus completed all treatment as planned, whereas more patients completed planned treatment with placebo—225 of 351 (64%).
The researchers found that adjuvant everolimus resulted in significant recurrence-free survival improvement in the intent-to-treat and per-protocol cohorts. Grade ≥ 3 adverse events were more frequent in the patients receiving everolimus (42%) vs placebo (8%).
“EVEREST remains the only phase III adjuvant renal cell carcinoma trial of an mTOR inhibitor. In patients with clear cell renal cell carcinoma at very high risk for recurrence, adjuvant everolimus was associated with significantly improved recurrence-free survival vs placebo in a subset of patients comparable to those in [placebo-controlled phase III trials of sunitinib] S-TRAC and [pembrolizumab] KN546. These results can inform the design and development of future adjuvant trials in high-risk renal cell carcinoma,” concluded the study authors.
“The focus on patients with clear cell renal cell carcinoma at very high risk for recurrence allows researchers to better interpret the results of EVEREST in the context of the modestly positive S-TRAC and KN546 trials,” said Dr. Lara, Distinguished Professor of Medicine and Executive Associate Dean for Cancer Programs at the University of California Davis School of Medicine as well as Co–Chair-Elect of the SWOG Cancer Research Network.
Disclosure: Funding for this study was provided by the National Institutes of Health, the National Cancer Institute, and Novartis Pharmaceuticals Corporation. For full disclosures of the study authors, visit cslide.ctimeetingtech.com/esmo2023.
