CheckMate-9ER: Nivolumab plus Cabozantinib Extends Progression-Free Survival and Overall Survival Compared with Sunitinib

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

References

1. 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.
2. 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.