Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma
- PMID: 33657295
- PMCID: PMC8436591
- DOI: 10.1056/NEJMoa2026982
Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma
Abstract
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.).
Copyright © 2021 Massachusetts Medical Society.
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Comment in
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Re: Nivolumab plus Cabozantinib Versus Sunitinib for Advanced Renal-cell Carcinoma.Eur Urol. 2021 Aug;80(2):256-257. doi: 10.1016/j.eururo.2021.04.039. Epub 2021 May 13. Eur Urol. 2021. PMID: 33992475 No abstract available.
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Fortgeschrittenes Nierenzellkarzinom: Nivolumab/Cabozantinib versus Sunitinib.Aktuelle Urol. 2022 Feb;53(1):16-18. doi: 10.1055/a-1559-4893. Epub 2022 Jan 25. Aktuelle Urol. 2022. PMID: 35078256 German. No abstract available.
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Cost Effectiveness of Treatment Sequences in Advanced Renal Cell Carcinoma.Eur Urol Oncol. 2023 Jun;6(3):331-338. doi: 10.1016/j.euo.2023.01.011. Epub 2023 Feb 14. Eur Urol Oncol. 2023. PMID: 36797084
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