Everolimus Fails to Improve RFS, OS in Patients With nccRCC

A recent study from Shuchi Gulati, MD, MSc, and colleagues published in JAMA Network Open sought to determine the effects of adjuvant everolimus following nephrectomy on recurrence-free survival (RFS) and overall survival (OS) in patients with non–clear cell renal cell carcinoma (nccRCC).

Researchers performed a subgroup analysis of the phase 3, randomized, EVEREST trial of patients who received treatment with everolimus from April 2011 to September 2016. Patients included in the trial presented with fully resected RCC at either intermediate-high risk or very-high risk for recurrence and had undergone radical or partial nephrectomy.

Participating patients either underwent 54 weeks of treatment with everolimus 10 mg per day or treatment with a matching placebo.

The primary endpoints included RFS, OS, and the rates of adverse events. Investigators used a Cox regression model to estimate the hazard ratio (HR) for the treatment effect in OS and RFS.

Among the 1545 participants, 109 had papillary RCC, and 99 had chromophobe RCC. Of the 57 patients with papillary RCC who underwent treatment with everolimus, 26 finished the treatment regimen, and 26 of the patients with chromophobe RCC completed treatment.

Dr. Gulati and colleagues found that adjuvant everolimus did not improve RFS when compared with the placebo in either papillary (5-year RFS, 62% vs 70%; HR, 1.19; 95% CI, 0.61-2.33; P=.61) or chromophobe RCC (5-year RFS, 79% vs 77%; HR, 0.89; 95% CI, 0.37-2.13; P=.79).

Nine percent of patients who received the placebo experienced grade 3 or higher adverse events, compared with 48% of patients who received everolimus.

“In this clinical trial assessing the use of adjuvant everolimus, postoperative everolimus did not show evidence of improved RFS among patients with papillary or chromophobe RCC, and results from the study do not support adjuvant everolimus for this cohort,” the researchers wrote. “However, since the lower bounds of the 95% CIs were 0.61 and 0.89, respectively, potential treatment benefit in these subgroups cannot be ruled out.”