Nivolumab versus everolimus in advanced renal-cell carcinoma Journal Article

Authors: Motzer, R. J.; Escudier, B.; McDermott, D. F.; George, S.; Hammers, H. J.; Srinivas, S.; Tykodi, S. S.; Sosman, J. A.; Procopio, G.; Plimack, E. R.; Castellano, D.; Choueiri, T. K.; Gurney, H.; Donskov, F.; Bono, P.; Wagstaff, J.; Gauler, T. C.; Ueda, T.; Tomita, Y.; Schutz, F. A.; Kollmannsberger, C.; Larkin, J.; Ravaud, A.; Simon, J. S.; Xu, L. A.; Waxman, I. M.; Sharma, P.
Article Title: 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. Copyright © 2015 Massachusetts Medical Society.
Keywords: survival; adolescent; adult; cancer chemotherapy; cancer survival; controlled study; protein expression; treatment outcome; aged; aged, 80 and over; middle aged; survival analysis; young adult; major clinical study; overall survival; clinical trial; fatigue; mortality; sorafenib; advanced cancer; diarrhea; drug efficacy; drug safety; antineoplastic agents; comparative study; antineoplastic agent; progression free survival; quality of life; anemia; mucosa inflammation; nausea; randomized controlled trial; stomatitis; kidney carcinoma; kidney neoplasms; monoclonal antibody; coughing; dyspnea; hyperglycemia; pneumonia; pruritus; rash; antibodies, monoclonal; carcinoma, renal cell; multicenter study; drug response; antiangiogenic therapy; pazopanib; peripheral edema; phase 3 clinical trial; axitinib; epistaxis; everolimus; rapamycin; sirolimus; hypertriglyceridemia; dysgeusia; programmed death 1 ligand 1; decreased appetite; comparative effectiveness; cancer prognosis; nivolumab; very elderly; humans; human; male; female; priority journal; article; analogs and derivatives
Journal Title: New England Journal of Medicine
Volume: 373
Issue: 19
ISSN: 0028-4793
Publisher: Massachusetts Medical Society  
Date Published: 2015-11-05
Start Page: 1803
End Page: 1813
Language: English
DOI: 10.1056/NEJMoa1510665
PUBMED: 26406148
PROVIDER: scopus
PMCID: PMC5719487
Notes: Export Date: 2 December 2015 -- Source: Scopus
Citation Impact
MSK Authors
  1. Robert Motzer
    950 Motzer