TY - JOUR
T1 - Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma
AU - CheckMate 9ER Investigators
AU - Choueiri, T. K.
AU - Powles, T.
AU - Burotto, Mauricio
AU - Escudier, B.
AU - Bourlon, M. T.
AU - Zurawski, B.
AU - Juárez, V. M.Oyervides
AU - Hsieh, J. J.
AU - Basso, U.
AU - Shah, A. Y.
AU - Suárez, C.
AU - Hamzaj, A.
AU - Goh, J. C.
AU - Barrios, C.
AU - Richardet, M.
AU - Porta, C.
AU - Kowalyszyn, R.
AU - Feregrino, J. P.
AU - Zolnierek, J.
AU - Pook, D.
AU - Kessler, E. R.
AU - Tomita, Y.
AU - Mizuno, R.
AU - Bedke, J.
AU - Zhang, J.
AU - Maurer, M. A.
AU - Simsek, B.
AU - Ejzykowicz, F.
AU - Schwab, G. M.
AU - Apolo, A. B.
AU - Motzer, R. J.
N1 - Funding Information:
Supported by Bristol Myers Squibb in collaboration with Ono Pharmaceutical and with Exelixis, Ipsen Pharma, and Takeda Pharmaceutical. The authors received no financial support or compensation for publication of this manuscript. Dr. Choueiri is supported in part by the Dana–Farber/Harvard Cancer Center Kidney Specialized Program of Research Excellence, the Kohl-berg Chair at Harvard Medical School, the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at Dana–Farber Cancer Institute and by various grants from the National Cancer Institute, Department of Defense, and foundations. Patients treated at the Memorial Sloan Kettering Cancer Center were supported in part by a Cancer Center Support Grant–Core Grant (P30 CA008748). The University of Texas M.D. Anderson Cancer Center is supported by a National Institutes of Health Core Grant (P30 CA016672).
Publisher Copyright:
Copyright © 2021 Massachusetts Medical Society.
PY - 2021/3/4
Y1 - 2021/3/4
N2 - BACKGROUND The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known. METHODS In this phase 3, randomized, open-label trial, we randomly assigned adults with previously untreated clear-cell, advanced renal-cell carcinoma to receive either nivolumab (240 mg every 2 weeks) plus cabozantinib (40 mg once daily) or sunitinib (50 mg once daily for 4 weeks of each 6-week cycle). The primary end point was progression-free survival, as determined by blinded independent central review. Secondary end points included overall survival, objective response as determined by independent review, and safety. Health-related quality of life was an exploratory end point. RESULTS Overall, 651 patients were assigned to receive nivolumab plus cabozantinib (323 patients) or sunitinib (328 patients). At a median follow-up of 18.1 months for overall survival, the median progression-free survival was 16.6 months (95% confidence interval [CI], 12.5 to 24.9) with nivolumab plus cabozantinib and 8.3 months (95% CI, 7.0 to 9.7) with sunitinib (hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.64; P<0.001). The probability of overall survival at 12 months was 85.7% (95% CI, 81.3 to 89.1) with nivolumab plus cabozantinib and 75.6% (95% CI, 70.5 to 80.0) with sunitinib (hazard ratio for death, 0.60; 98.89% CI, 0.40 to 0.89; P = 0.001). An objective response occurred in 55.7% of the patients receiving nivolumab plus cabozantinib and in 27.1% of those receiving sunitinib (P<0.001). Efficacy benefits with nivolumab plus cabozantinib were consistent across subgroups. Adverse events of any cause of grade 3 or higher occurred in 75.3% of the 320 patients receiving nivolumab plus cabozantinib and in 70.6% of the 320 patients receiving sunitinib. Overall, 19.7% of the patients in the combination group discontinued at least one of the trial drugs owing to adverse events, and 5.6% discontinued both. Patients reported better health-related quality of life with nivolumab plus cabozantinib than with sunitinib. CONCLUSIONS Nivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol Myers Squibb and others; CheckMate 9ER ClinicalTrials.gov number, NCT03141177.).
AB - BACKGROUND The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known. METHODS In this phase 3, randomized, open-label trial, we randomly assigned adults with previously untreated clear-cell, advanced renal-cell carcinoma to receive either nivolumab (240 mg every 2 weeks) plus cabozantinib (40 mg once daily) or sunitinib (50 mg once daily for 4 weeks of each 6-week cycle). The primary end point was progression-free survival, as determined by blinded independent central review. Secondary end points included overall survival, objective response as determined by independent review, and safety. Health-related quality of life was an exploratory end point. RESULTS Overall, 651 patients were assigned to receive nivolumab plus cabozantinib (323 patients) or sunitinib (328 patients). At a median follow-up of 18.1 months for overall survival, the median progression-free survival was 16.6 months (95% confidence interval [CI], 12.5 to 24.9) with nivolumab plus cabozantinib and 8.3 months (95% CI, 7.0 to 9.7) with sunitinib (hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.64; P<0.001). The probability of overall survival at 12 months was 85.7% (95% CI, 81.3 to 89.1) with nivolumab plus cabozantinib and 75.6% (95% CI, 70.5 to 80.0) with sunitinib (hazard ratio for death, 0.60; 98.89% CI, 0.40 to 0.89; P = 0.001). An objective response occurred in 55.7% of the patients receiving nivolumab plus cabozantinib and in 27.1% of those receiving sunitinib (P<0.001). Efficacy benefits with nivolumab plus cabozantinib were consistent across subgroups. Adverse events of any cause of grade 3 or higher occurred in 75.3% of the 320 patients receiving nivolumab plus cabozantinib and in 70.6% of the 320 patients receiving sunitinib. Overall, 19.7% of the patients in the combination group discontinued at least one of the trial drugs owing to adverse events, and 5.6% discontinued both. Patients reported better health-related quality of life with nivolumab plus cabozantinib than with sunitinib. CONCLUSIONS Nivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol Myers Squibb and others; CheckMate 9ER ClinicalTrials.gov number, NCT03141177.).
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Anilides/administration & dosage
KW - Antineoplastic Agents/adverse effects
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - B7-H1 Antigen/antagonists & inhibitors
KW - Carcinoma, Renal Cell/drug therapy
KW - Female
KW - Humans
KW - Intention to Treat Analysis
KW - Kidney Neoplasms/drug therapy
KW - Male
KW - Middle Aged
KW - Nivolumab/administration & dosage
KW - Progression-Free Survival
KW - Proportional Hazards Models
KW - Pyridines/administration & dosage
KW - Quality of Life
KW - Receptor Protein-Tyrosine Kinases/antagonists & inhibitors
KW - Sunitinib/adverse effects
KW - Survival Analysis
KW - Adult
KW - Aged
KW - 80 and over
KW - Anilides
KW - Antineoplastic Agents
KW - Antineoplastic Combined Chemotherapy Protocols
KW - B7-H1 Antigen
KW - Carcinoma
KW - Renal Cell
KW - Female; Humans
KW - Intention to Treat Analysis
KW - Kidney Neoplasms
KW - Male
KW - Middle Aged
KW - Nivolumab
KW - Progression-Free Survival
KW - Proportional Hazards Models
KW - Pyridines
KW - Quality of Life
KW - Receptor Protein-Tyrosine Kinases
KW - Sunitinib
KW - Survival Analysis
UR - http://www.scopus.com/inward/record.url?scp=85102482162&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2026982
DO - 10.1056/NEJMoa2026982
M3 - Article
C2 - 33657295
AN - SCOPUS:85102482162
SN - 0028-4793
VL - 384
SP - 829
EP - 841
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 9
ER -