N Engl J Med 2015 Nov 25;373(19):1803-13. Epub 2015 Sep 25.
From Memorial Sloan Kettering Cancer Center, New York (R.J.M.), and Roswell Park Cancer Institute, Buffalo (S.G.) - both in New York; Institut Gustave Roussy, Villejuif (B.E.), and Bordeaux University Hospital, Hôpital Saint André, Bordeaux (A.R.) - both in France; Beth Israel Deaconess Medical Center (D.F.M.) and Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School (T.K.C.) - all in Boston; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore (H.J.H.); Stanford Cancer Institute, Stanford, CA (S.S.); University of Washington and Fred Hutchinson Cancer Research Center, Seattle (S.S.T.); Vanderbilt University Medical Center, Nashville (J.A.S.); Fondazione Istituto Nazionale Tumori, Milan (G.P.); Fox Chase Cancer Center, Philadelphia (E.R.P.); Hospital Universitario 12 De Octubre, Madrid (D.C.); Westmead Hospital and Macquarie University, Sydney (H.G.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Helsinki University Central Hospital and University of Helsinki, Helsinki (P.B.); South West Wales Cancer Institute and Swansea University College of Medicine, Swansea (J.W.), and Royal Marsden Hospital, London (J.L.) - both in the United Kingdom; University Hospital Essen of University of Duisburg-Essen, Germany (T.C.G.); Chiba Cancer Center, Chiba (T.U.), and Niigata University, Niigata (Y.T.) - both in Japan; Hospital Sao Jose, Beneficencia Portuguesa de São Paulo, São Paulo (F.A.S.); British Columbia Cancer Agency, Vancouver, BC, Canada (C.K.); Bristol-Myers Squibb, Lawrenceville (J.S.S., I.M.W.) and Hopewell (L.-A.X.) - both in New Jersey; and M.D. Anderson Cancer Center, University of Texas, Houston (P.S.).
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.).