Bradley McGregor, MD of the Dana-Farber Cancer Institute speaks about Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma.
Link to Article:
https://www.nejm.org/doi/full/10.1056/NEJMoa2026982?query=TOC
Synopsis:
BACKGROUND: In the treatment of previously untreated advanced renal-cell carcinoma, the efficacy and protection of nivolumab plus cabozantinib have not been compared to those of sunitinib.
METHODS: 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 in this phase 3 randomized, open-label study (50 mg once daily for 4 weeks of each 6-week cycle). The primary outcome measure was progression-free survival, which was calculated by a blinded central study. Overall survival, objective response as decided by independent analysis, and protection were all secondary endpoints. An exploratory endpoint was health-related quality of life.
RESULTS:
A total of 651 patients were randomly allocated to receive either nivolumab plus cabozantinib (323 patients) or sunitinib (323 patients) (328 patients). The median progression-free survival was 16.6 months (95 percent confidence interval [CI], 12.5 to 24.9) with nivolumab plus cabozantinib and 8.3 months (95 percent CI, 7.0 to 9.7) with sunitinib at a median follow-up of 18.1 months for overall survival (hazard ratio for disease progression or death, 0.51; 95 percent CI, 0.41 to 0.64; P0.001). With nivolumab plus cabozantinib, the likelihood of overall survival at 12 months was 85.7 percent (95 percent CI, 81.3 to 89.1), and with sunitinib, it was 75.6 percent (95 percent CI, 70.5 to 80.0) (hazard ratio for death, 0.60; 98.89 percent CI, 0.40 to 0.89; P=0.001). Patients who received nivolumab plus cabozantinib had a 55.7 percent objective response, while those who received sunitinib had a 27.1 percent objective response (P0.001). The benefits of nivolumab plus cabozantinib in terms of efficacy were consistent across subgroups. 75.3 percent of the 320 patients who received nivolumab plus cabozantinib and 70.6 percent of the 320 patients who received sunitinib experienced adverse events of some cause of grade 3 or higher. Overall, 19.7% of patients in the combination group stopped taking at least one of the trial medications due to side effects, and 5.6 percent stopped taking both. Patients who received nivolumab plus cabozantinib showed a higher health-related quality of life than those who received sunitinib.
FINDINGS:
In patients with previously untreated advanced renal-cell carcinoma, nivolumab plus cabozantinib outperformed sunitinib in terms of progression-free survival, overall survival, and the probability of response. (CheckMate 9ER ClinicalTrials.gov number: NCT03141177; sponsored by Bristol Myers Squibb and others.) (This connection will open in a new tab.)