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Cabozantinib plus nivolumab and ipililumab improves PFS in advanced RCC subgroups


The median progression-free survival (PFS) was 16.9 months (95% CI, 11.5-not estimable) with cabozantinib vs 11.3 months (95% CI, 7.7-14.0) with placebo in the PFS intention-to-treat population.

A recently presented study found that frontline use of cabozantinib (Cabometyx) in combination with nivolumab (Opdivo) and ipilimumab (Yervoy) is associated with improved survival in the treatment of intermediate- or poor-risk advanced renal cell cancer (RCC).1

Thomas Powles, MD

Thomas Powles, MD

The finding is part of updated data from the phase 3 COSMIC-313 study (NCT03937219) that were presented at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium. The authors were led by Thomas Powles, MD, of Barts Cancer Centre at St. Bartholomew's Hospital in London, United Kingdom.

The median progression-free survival (PFS) was 16.9 months (95% CI, 11.5-not estimable [NE]) with cabozantinib vs 11.3 months (95% CI, 7.7-14.0) with placebo in the PFS intention-to-treat population (HR, 0.74; 95% CI, 0.58-0.94)), which was conducted after 20.2 months of median follow-up. A survival benefit was also observed in the intent-to-treat (ITT) population, with median PFS values of 15.3 months (95% CI, 12.7-22.5) and 11.3 months (95% CI, 9.3-14.0) in the experimental and placebo groups, respectively (HR, 0.74; 95% CI, 0.61-14.0), after 17.7 months of median follow-up.

Among patients with intermediate-risk disease in the ITT population, median PFS was 17.9 months in the cabozantinib arm (95% CI, 14.1- NE) vs 11.3 months (95% CI, 8.4-15.3) in the placebo arm (HR, 0.68; 95% CI, 0.54-0.86). For those with poor-risk disease the median PFS was 9.5 months (95% CI, 8.3-15.8) in the cabozantinib arm and 11.2 months (95% CI, 6.0-14.2) in the placebo arm (HR, 0.93; 95% CI, 0.64-1.35).

The objective response rate (ORR) was 45% in the intermediate-risk subgroup among those treated with cabozantinib vs 36% among those treated with placebo. The disease control rate (DCR) meanwhile was 88% and 74% in the experimental and placebo groups, respectively.

The ORR for the poor-risk group was 36% in the experimental group and 38% in the placebo group, and the DCR was 79% and 68%, respectively.

COSMIC-313 enrolled 855 patients with intermediate- or poor-risk RCC according to International Metastatic RCC Database Consortium (IMDC) criteria. They were randomly assigned 1:1 to receive either cabozantinib at 40 mg by mouth daily or a matched placebo. Both treatment groups also received intravenous nivolumab at 3 mg/kg and intravenous ipilimumab at 1 mg/kg every 3 weeks for 4 cycles followed by nivolumab at 480 mg every 4 weeks for up to 2 years and cabozantinib at 40 mg by mouth daily.

Roughly 75% of patients were classified as having intermediate-risk disease, with the remaining 25% having poor-risk disease. Most patients in all subgroups had a tumor PD-L1 status smaller than 1%. Most patients in the intermediate-risk subgroup had a Karnofsky performance status of 90 or 100, whereas most in the poor-risk had a status of 70 or 80.

Nearly all patients experienced some kind of treatment-related adverse effect (TRAE). The incidence of grade 3/4 TRAEs was 74% across patients with intermediate-risk disease in the experimental group vs 42% across those in the placebo group. The corresponding values were 67% and 38%, respectively, across the poor-risk subgroup. Grade 5 TRAEs occurred in 1% of patients in each group for the intermediate-risk subgroup and 1% vs 2% in the poor-risk subgroup for those in the combination and placebo arms, respectively. Total treatment discontinuation due to TRAEs occurred in 14% of those treated with cabozantinib vs 5% of those treated with placebo in the intermediate-risk subgroup; it occurred in 5% vs 4% in the poor-risk subgroup.

Regarding overall survival data, follow-up is still ongoing.


1. Powles T, Motzer RJ, Albiges L, et al. Outcomes by IMDC risk in the COSMIC-313 phase 3 trial evaluating cabozantinib (C) plus nivolumab (N) and ipilimumab (I) in first-line advanced RCC (aRCC) of IMDC intermediate or poor risk. J Clin Oncol. 2023;41(suppl 6):605. doi:10.1200/JCO.2023.41.6_suppl.605

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