Adjuvant everolimus improves RFS in patients with very high-risk ccRCC

In patients with very high-risk clear cell renal cell carcinoma (ccRCC), treatment with everolimus (Afinitor) following surgery led to significant improvements in recurrence-free survival (RFS) vs placebo, according to a secondary analysis from the phase 3 SWOG S0931 EVEREST trial (NCT01120249) presented at the 2023 European Society for Medical Oncology (ESMO) Annual Congress in Madrid, Spain.¹

“The focus on patients with clear cell RCC 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,” says Primo N. Lara Jr, MD.

The initial trial results from EVEREST were published earlier this year and showed no improvement in RFS with everolimus vs placebo in patients who had RCC with a high risk of recurrence.² The secondary analysis from the study, presented at ESMO, focused on a subset of patients whose RCC was of clear cell histology and were considered to be in the very high-risk category.

In total, 699 patients met the inclusion criteria and were included for analysis. Patients were randomly assigned 1:1 to receive 10 mg everolimus once daily (n = 348) or placebo (n = 351) for 54 weeks. Patient characteristics were similar among both cohorts.

Data showed a 20% reduced risk of recurrence or death among patients who received everolimus compared with placebo (HR, 0.80; 95% CI, 0.65-0.99; P = .040), with improvements in RFS seen in both the intent-to-treat and per-protocol cohorts. Overall survival, per 5-year Kaplan Meier estimate, was 85% in the experimental arm, compared with 81% in the control arm (HR, 0.85; 95% CI 0.64-1.14; P = .28).

Overall, 42% of patients who received everolimus experienced grade 3 or higher adverse events (AEs), compared with 8% among those in the placebo arm. Patients in the everolimus cohort were also more likely to discontinue treatment, with only 47% of patients in the experimental arm completing treatment as planned, compared with 64% of patients in the control arm.

According to a news release on the findings, the EVEREST study is the only phase 3 trial of an mTOR inhibitor as adjuvant therapy in patients with RCC.3Previously, only 2 other trials have published promising results with adjuvant therapy in RCC: S-TRAC and KN546. The patients included in the EVEREST trial are comparable to those included in the 2 previous trials.

“The focus on patients with clear cell RCC 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,” Primo N. Lara Jr, MD, said in the news release.³ Lara, who presented the EVEREST findings at ESMO, is a distinguished professor of medicine and the executive associate dean for cancer programs at the University of California Davis School of Medicine, as well as the director of the UC Davis Comprehensive Cancer Center.

In the poster presentation of the EVEREST data, Lara indicated that these findings may help inform the design and development of future adjuvant trials in this patient population.

References

1. Adjuvant everolimus (EVE) in patients (pts) with completely resected very high-risk renal cell cancer (RCC) and clear cell histology: Results from the phase III SWOG S0931 (EVEREST) trial. Presented at the European Society of Medical Oncology (ESMO) Congress. October 20-24, 2023. Madrid, Spain. Abstract 1887P

2. Ryan CW, Tangen CM, Heath EI, et al. Adjuvant everolimus after surgery for renal cell carcinoma (EVEREST): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet. 2023;402(10407):1043-1051. doi:10.1016/S0140-6736(23)00913-3

3. Highest risk patients with clear-cell renal cell carcinoma benefit from adjuvant everolimus. News release. Southwest Oncology Group (SWOG). October 23, 2023. Accessed October 25, 2023. https://www.newswise.com/articles/highest-risk-patients-with-clear-cell-renal-cell-carcinoma-benefit-from-adjuvant-everolimus