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Clinical Trial
. 2015 Nov 5;373(19):1803-13.
doi: 10.1056/NEJMoa1510665. Epub 2015 Sep 25.

Nivolumab Versus Everolimus in Advanced Renal-Cell Carcinoma

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Free PMC article
Clinical Trial

Nivolumab Versus Everolimus in Advanced Renal-Cell Carcinoma

Robert J Motzer et al. N Engl J Med. .
Free PMC article

Abstract

Background: Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment.

Methods: A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily. The primary end point was overall survival. The secondary end points included the objective response rate and safety.

Results: The median overall survival was 25.0 months (95% confidence interval [CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 23.1) with everolimus. The hazard ratio for death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.002), which met the prespecified criterion for superiority (P≤0.0148). The objective response rate was greater with nivolumab than with everolimus (25% vs. 5%; odds ratio, 5.98 [95% CI, 3.68 to 9.72]; P<0.001). The median progression-free survival was 4.6 months (95% CI, 3.7 to 5.4) with nivolumab and 4.4 months (95% CI, 3.7 to 5.5) with everolimus (hazard ratio, 0.88; 95% CI, 0.75 to 1.03; P=0.11). Grade 3 or 4 treatment-related adverse events occurred in 19% of the patients receiving nivolumab and in 37% of the patients receiving everolimus; the most common event with nivolumab was fatigue (in 2% of the patients), and the most common event with everolimus was anemia (in 8%).

Conclusions: Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.).

Figures

Figure 1
Figure 1
Kaplan–Meier Curve for Overall Survival.
Figure 2
Figure 2
Overall Survival According to Subgroup Analyses (A) and Kaplan–Meier Curve for Progression-Free Survival (B).
Figure 2
Figure 2
Overall Survival According to Subgroup Analyses (A) and Kaplan–Meier Curve for Progression-Free Survival (B).
Figure 3
Figure 3
Kaplan–Meier Curve for Overall Survival by PD-L1 Expression ≥1% (A) and PD-L1 Expression <1% (B).

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