Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.

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.).

• Authors: Robert J Motzer, Bernard Escudier, David F McDermott, Saby George, Hans J Hammers, Sandhya Srinivas, Scott S Tykodi, Jeffrey A Sosman, Giuseppe Procopio, Elizabeth R Plimack, Daniel Castellano, Toni K Choueiri, Howard Gurney, Frede Donskov, Petri Bono, John Wagstaff, Thomas C Gauler, Takeshi Ueda, Yoshihiko Tomita, Fabio A Schutz, Christian Kollmannsberger, James Larkin, Alain Ravaud, Jason S Simon, Li-An Xu, Ian M Waxman, Padmanee Sharma, CheckMate 025 Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 373 Issue 19 Pg. 1803-13 (Nov 05 2015) ISSN: 1533-4406 [Electronic] United States
• PMID: 26406148 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• Nivolumab
• Everolimus
• Sirolimus

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Carcinoma, Renal Cell (drug therapy, mortality)
• Everolimus
• Female
• Humans
• Kidney Neoplasms (drug therapy, mortality)
• Male
• Middle Aged
• Nivolumab
• Quality of Life
• Sirolimus (adverse effects, analogs & derivatives, therapeutic use)
• Survival Analysis
• Young Adult