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Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma
Open accessAbstract
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.).
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Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534
Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012
Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Parkin, D. M., Forman, D., & Bray, F. (2015) · International Journal of Cancer · doi:10.1002/ijc.29210 · Cited by 28,766
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
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O'Brien, P. C., & Fleming, T. R. (1979) · Biometrics · doi:10.2307/2530245 · Cited by 3,311
Brahmer, J. R., Drake, C. G., WOLLNER, I. S., Powderly, J. D., Picus, J., Sharfman, W. H., Stankevich, E., Pons, A., Salay, T. M., McMiller, T. L., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.7609 · Cited by 2,967
Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Escudier, B. J., Porta, C., Schmidinger, M., Ferran Algaba, B., Patard, J., Khoo, V. S., Eisen, T. G., & Horwich, A. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu259 · Cited by 2,253
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Schag, C. C., Heinrich, R. L., & Ganz, P. A. (1984) · Journal of Clinical Oncology · doi:10.1200/jco.1984.2.3.187 · Cited by 1,521
Hamanishi, J., Mandai, M., Iwasaki, M., Okazaki, T., Tanaka, Y., Yamaguchi, K., Higuchi, T., Yagi, H., Takakura, K., Minato, N., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611533104 · Cited by 1,378
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Brookmeyer, R., & Crowley, J. (1982) · Biometrics · doi:10.2307/2530286 · Cited by 914
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Metadata
- 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.
- Affiliations
- Brigham and Women's Hospital (US)
- Institut Gustave Roussy (FR)
- Beth Israel Deaconess Medical Center (US)
- Roswell Park Comprehensive Cancer Center (US)
- Sidney Kimmel Comprehensive Cancer Center (US)
- Stanford Cancer Institute (US)
- University of Washington (US)
- Vanderbilt University Medical Center (US)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Fox Chase Cancer Center (US)
- Hospital Universitario 12 De Octubre (ES)
- Westmead Hospital (AU)
- Aarhus University Hospital (DK)
- University of Helsinki (FI)
- Swansea University (GB)
- Essen University Hospital (DE)
- Chiba Cancer Center (JP)
- Niigata University (JP)
- Beneficência Portuguesa de São Paulo (BR)
- BC Cancer Agency (CA)
- Royal Marsden Hospital (GB)
- Centre Hospitalier Universitaire de Bordeaux (FR)
- Bristol-Myers Squibb (United States) (US)
- The University of Texas MD Anderson Cancer Center (US)
- ORCID
- Motzer, Robert J.
- Escudier, Bernard
- McDermott, David F.
- George, Saby
- Hammers, Hans J.
- Tykodi, Scott S.
- Sosman, Jeffrey A.
- Procopio, Giuseppe
- Plimack, Elizabeth R.
- Castellano, Daniel
- Choueiri, Toni K.
- Gurney, Howard
- Donskov, Frede
- Bono, Petri
- Wagstaff, John
- Gauler, Thomas C.
- Ueda, Takeshi
- Tomita, Yoshihiko
- Schutz, Fabio A.
- Kollmannsberger, Christian
- Larkin, James
- Ravaud, Alain
- Sharma, Padmanee
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2015-11-05
- Volume
- 373
- Issue
- 19
- Pages
- 1803-1813
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC5719487
- OpenAlex
- W2222086386
- Cited by
- 5,807
- References
- 36
- Citations by year
- 2026: 173 · 2025: 255 · 2024: 367 · 2023: 449 · 2022: 535 · 2021: 669 · 2020: 723 · 2019: 669 · 2018: 719 · 2017: 691 · 2016: 511 · 2015: 36
- FWCI
- 515.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- Lirias (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- National Cancer Institute (P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Keywords
- nivolumab, everolimus, PD-1 inhibitors, mTOR inhibitors, overall survival, objective response rate, progression-free survival, treatment-related adverse events, anti-angiogenic therapy, immune checkpoint inhibitors, mTOR inhibition, fatigue, anemia, previously treated patients
- MeSH terms
- Everolimus, Nivolumab, Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Agents, Carcinoma, Renal Cell, Female, Humans, Kidney Neoplasms, Male, Middle Aged, Quality of Life, Survival Analysis, Sirolimus, Young Adult
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