1. The combination of nivolumab and cabozantinib was superior to sunitinib in untreated advanced renal-cell carcinoma
2. The combination treatment caused more drug discontinuation compared to sunitinib.
Evidence Rating Level: 1 (Excellent)
Study Rundown: In advanced renal-cell carcinoma, sunitinib is the standard of care, but the landscape of different regimens is evolving. Previous trials of single-agent cabozantinib, a tyrosine kinase inhibitor (TKI), and nivolumab, a programmed death 1 (PD-1) immune checkpoint inhibitor, have been effective as the first-line treatment. This trial compared the combination of nivolumab and cabozantinib to sunitinib. The combination treatment improved overall survival, progression-free survival, and higher objective response rates. Additionally, grade 3 or above adverse events and study drug discontinuation occurred more often in the combination group. Quality of life was better maintained in the combination group compared to the sunitinib group. Study limitations included median overall survival was not reached in both groups. Overall, this trial showed the superiority of the combination treatment in advanced renal-cell carcinoma.
In-Depth [randomized controlled trial]: This phase 3, randomized, open-label clinical trial enrolled 651 patients at 125 sites in 18 countries. Patients diagnosed with untreated advanced renal cell carcinoma with a clear cell component and who received no previous systemic therapies were included in the study. Patients with active central nervous system metastases or active autoimmune disease were excluded from the study. Patients were randomized in a 1:1 ratio to either nivolumab and cabozantinib or sunitinib, respectively. The median follow-up was 18.1 months. The combination group had superior overall survival (hazard ratio [HR], 0.6; 95% confidence interval [CI], 0.40 to 0.89), progression-free survival (HR, 0.51; 95% CI, 0.41 to 0.64), and objective response (combination group, 55.7%; sunitinib group, 27.1%; P < 0.001). FKSI-19 (Functional Assessment of Cancer Therapy-Kidney Symptom Index), a measure of the quality of life, was higher in the combination group (P < 0.05). Grade 3 or above adverse events occurred in 75.3% of patients in the combination group and 70.6% of the sunitinib group. Finally, 19.7% of patients in the PD-L1/TKI group discontinued a study medication and 16.9% stopped the treatment in the sunitinib group. Overall, the combination regiment is a viable option as first-line treatment for carefully selected patients.
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