Everolimus Shows Promise in Patients with Very-High-Risk Clear Cell Renal Cell Carcinoma After Surgery


A secondary analysis from the SWOG S0931 EVEREST trial has revealed encouraging results for patients with very-high-risk clear cell renal cell carcinoma (RCC) who were treated with everolimus after surgery. The findings, set to be presented at the European Society of Medical Oncology (ESMO) Congress 2023, demonstrate a statistically significant improvement in recurrence-free survival compared to patients receiving placebo after surgery.

The study, led by distinguished professor Primo N. Lara Jr., MD, and sponsored by the National Cancer Institute (NCI)-funded SWOG Cancer Research Network, enrolled over 1,500 patients with either clear-cell or non-clear-cell RCC who were considered to be at intermediate or very high risk of disease recurrence. Participants were randomly assigned to receive one year of either everolimus or placebo after surgery.

Earlier this year, the primary results of the SWOG S0931 trial were published in The Lancet, which showed that although patients on the everolimus arm had a longer recurrence-free survival time, the difference narrowly missed the criterion for statistical significance. However, the newly presented secondary analysis focused specifically on patients with clear-cell histology RCC, who were categorized as being at very high risk for disease recurrence.

Among the subgroup of 699 eligible patients in this analysis, those who received everolimus had a 20 percent lower risk of disease recurrence or death compared to those who received placebo (hazard ratio: 0.80; 95 percent confidence interval: 0.65-0.99; two-sided P value = 0.040).

Importantly, these patients in the subgroup had similar characteristics to those enrolled in the only two previous clinical trials of adjuvant therapy in RCC that reported positive results, namely the S-TRAC and KN546 studies, both of which led to Food and Drug Administration (FDA) approval of a drug.

While the results are promising, the analysis also highlighted the incidence of Grade 3 or higher adverse events (side effects), which were more frequent in the everolimus arm compared to the placebo arm (42 percent vs. 8 percent). Furthermore, patients in the everolimus arm were more likely to discontinue treatment, with only 47 percent of patients completing all planned treatment, compared to 64 percent of patients in the placebo arm.

The SWOG S0931 trial, supported by the NCI and the National Institutes of Health (NIH), is the only phase 3 trial investigating the use of an mTOR inhibitor as adjuvant therapy for patients with RCC. It is part of the NCI National Clinical Trials Network (NCTN) and aims to improve outcomes for RCC patients at high risk of disease recurrence.

The study, in addition to Lara, includes several co-authors from prestigious institutions such as Wayne State University/Karmanos Cancer Institute, Columbia University/Herbert Irving Cancer Center, University of California San Francisco, University of Michigan Rogel Comprehensive Cancer Center, City of Hope Comprehensive Cancer Center, Roswell Park Comprehensive Cancer Center, Loyola University Chicago Medical Center, Dana-Farber Cancer Institute, Huntsman Cancer Institute (University of Utah), Fox Chase Cancer Center (Temple Health), Abramson Cancer Center (University of Pennsylvania), UCLA School of Medicine, and Children’s Hospital of San Antonio.

In conclusion, the secondary analysis of the SWOG S0931 EVEREST trial has demonstrated the potential benefits of everolimus as adjuvant therapy for patients with very-high-risk clear cell RCC after surgery. These findings suggest a significant improvement in recurrence-free survival and offer hope for improving outcomes in this patient population. Further research and evaluation are warranted to validate these results and potentially pave the way for the FDA approval of everolimus as a postoperative treatment option for high-risk RCC patients.


  1. Source: Coherent Market Insights, Public sources, Desk research
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