Cabozantinib, a tyrosine kinase inhibitor, and nivolumab, an anti–PD-1 immunotherapy, are approved as single-agent therapies for advanced renal-cell carcinoma (RCC). The phase 3 CheckMate-9ER trial evaluated the efficacy of combination nivolumab plus cabozantinib in patients with previously untreated advanced RCC. A total of 651 patients were randomly assigned to receive once-daily cabozantinib 40 mg plus nivolumab 240 mg every 2 weeks or sunitinib 50 mg for 4 weeks followed by 2 weeks off treatment. Progression-free survival was the primary end point. Overall survival, objective response rate, and safety were key secondary end points.1
After a median follow-up of 18.1 months, cabozantinib plus nivolumab significantly improved median progression-free survival versus sunitinib (16.6 vs 8.3 months, respectively; hazard ratio, 0.51; 95% confidence interval, 0.41-0.64; P <.001). Combination therapy with cabozantinib plus nivolumab also improved the rate of overall survival at 12 months (85.7% vs 75.6%), resulting in a 40% improvement versus sunitinib (98.89% confidence interval, 11%-60%; P = .001).1
Confirmed objective response rate was 55.7% with nivolumab plus cabozantinib (8.0% complete response; 47.7% partial response) and 27.1% with sunitinib (4.6% complete response; 22.6% partial response). Among those patients with a response, the median duration was 20.2 months for nivolumab plus cabozantinib and 11.5 months for sunitinib.1
Grade 3 or 4 treatment-related adverse events were reported in 60.6% of patients treated with nivolumab plus cabozantinib and 50.9% of patients treated with sunitinib. In both groups, the most frequently reported grade 3 or 4 adverse events were hypertension (12.5% for nivolumab and cabozantinib vs 13.1% for sunitinib), palmar–plantar erythrodysesthesia (7.5% vs 7.5%, respectively), diarrhea (6.9% vs 4.4%, respectively), and elevated lipase levels (6.2% vs 4.7%, respectively). Discontinuation of ≥1 agents due to adverse events was reported for 19.7% of patients treated with nivolumab plus cabozantinib and 16.9% of patients treated with sunitinib.1
Whereas quality of life deteriorated with sunitinib, validated quality-of-life measures stayed relatively stable with nivolumab and cabozantinib.1
The study investigators concluded that nivolumab and cabozantinib improved survival in previously untreated metastatic RCC and, despite substantial adverse events, maintained quality of life.1 On the basis of the CheckMate-9ER trial results, cabozantinib and nivolumab were approved for use in patients with untreated advanced RCC in January 2021.2
- Choueiri TK, Powles T, Burotto M, et al; for the CheckMate 9ER Investigators. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021;384:829-841.
- US Food and Drug Administration. FDA approves nivolumab plus cabozantinib for advanced renal cell carcinoma. Updated January 22, 2021. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-plus-cabozantinib-advanced-renal-cell-carcinoma. Accessed November 18, 2021.