Outcomes When Cabozantinib Is Added to Ipilimumab/Nivolumab in Advanced Renal Cell Carcinoma

The immunotherapy doublet of ipilimumab and nivolumab along with a variety of tyrosine kinase inhibitor (TKI)/immune checkpoint inhibitor combinations are standard-of-care options for patients with advanced clear cell renal cancer with intermediate or poor prognostic risk according to the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) index.

In an industry-sponsored phase 3 study, 855 previously untreated patients with advanced renal cancer with a clear-cell component and intermediate or poor IMDC prognostic risk were randomized to receive the standard renal dose and schedule of nivolumab and ipilimumab plus either the TKI cabozantinib (40 mg/day) or placebo. The primary end point was progression-free survival (PFS) assessed by blinded, independent radiology review in the first 550 patients who underwent randomization. Patients' median age was approximately 60 years and 75% had IMDC intermediate prognostic risk.

The objective response rate was 43% in the cabozantinib group versus 36% in the control group. The probability of PFS at 12 months was 0.57 in the cabozantinib group compared with 0.49 in the control group (hazard ratio for disease progression or death, 0.73; 95% confidence interval, 0.57–0.94; P=0.01)

Grade 3 or 4 adverse events occurred in significantly more patients in the cabozantinib group than the control group (79% vs. 56%); transaminitis and hypertension were among the most common toxicities. Treatment-related adverse events led to discontinuation of a component of the trial regimen in 45% of the cabozantinib group and 24% of the control group.