Cabozantinib plus Nivolumab Improves Overall Survival in Advanced Kidney Cancer

In the initial management of metastatic clear-cell renal cell carcinoma, both the tyrosine kinase inhibitor (TKI) cabozantinib and the immune checkpoint inhibitor nivolumab have demonstrated improvement in overall survival as single agents. Investigators conducted an international randomized phase 3 trial comparing the combination of cabozantinib (40 mg/day) plus nivolumab (240 mg intravenously every 2 weeks) to a prior standard of care, the TKI sunitinib (50 mg/day; 4 weeks on, 2 weeks off). The primary endpoint was progression-free survival (PFS).

Of 651 patients with previously untreated metastatic renal cancer with a clear-cell component, approximately 80% had International Metastatic Renal-Cell Carcinoma Database good or intermediate risk scores and 11% had sarcomatoid features.

At a median follow-up of 18 months, median PFS was 16.6 in the combination group versus 8.3 months in the sunitinib group (hazard ratio, 0.51; P<0.001). At 12 months, the probability of PFS was 57.6% versus 36.9% in the combination and sunitinib groups, and overall survival was 85.7% versus 75.6% (HR, 0.60; P=0.001). Objective responses occurred in 55.7% versus 27.1% (P<0.001), respectively, with complete responses in 8.0% versus 4.6%. Grade 3 or higher adverse events of any cause were observed in 75.3% of the combination group and 70.6% of the sunitinib group; adverse events led to discontinuation of study agents in 19.7% and 16.9%, respectively.