Add-on cabozantinib confers survival benefit in advanced renal-cell carcinoma with caveat

For patients with treatment-naïve advanced renal-cell carcinoma who have intermediate or poor prognostic risk, adding cabozantinib to the combination of nivolumab and ipilimumab significantly prolongs progression-free survival (PFS) compared with the combination alone but at the expense of increased grade 3 or 4 adverse events (AEs), as shown in a phase III trial.

The study included 855 patients with advanced clear-cell renal-cell carcinoma who had not received previous treatment and had intermediate or poor prognostic risk according to the International Metastatic Renal-Cell Carcinoma Database Consortium categories. These patients were randomly assigned to treatment with nivolumab and ipilimumab in addition to either 40 mg of cabozantinib daily (experimental group, n=428) or matched placebo (control group, n=427).

Nivolumab (3 mg per kilogram of body weight) and ipilimumab (1 mg per kilogram) were given once every 3 weeks for four cycles. Afterwards, patients received nivolumab maintenance therapy (480 mg once every 4 weeks) for up to 2 years.

The primary endpoint of PFS was evaluated in the first 550 patients who had undergone randomization, including 276 in the experimental group and 274 in the control group. Add-on cabozantinib yielded a significant 27-percent reduction in the risk of disease progression or death compared with control treatment (hazard ratio for disease progression or death, 0.73, 95 percent confidence interval [CI], 0.57–0.94; p=0.01).

Response was documented in 43 percent of the patients in the experimental group and in 36 percent in the control group. Follow-up for the secondary endpoint of overall survival is ongoing.

In terms of safety, however, grade 3 or 4 AEs occurred more frequently among patients in the experimental group than those in the control group (79 percent vs 56 percent).