Cabozantinib Plus Nivolumab/Ipilimumab Shows Notable PFS Improvement in Intermediate-Risk, Advanced RCC

Supplements and Featured Publications2023 Genitourinary Cancers Symposium Meeting Reporter
Volume 1
Issue 1

The combination of frontline cabozantinib, nivolumab, and ipilimumab led to a greater improvement in progression-free survival in patients with intermediate- vs poor-risk advanced renal cell carcinoma.

The combination of frontline cabozantinib (Cabometyx), nivolumab (Opdivo), and ipilimumab (Yervoy) led to a greater improvement in progression-free survival (PFS) in patients with intermediate- vs poor-risk advanced renal cell carcinoma (RCC), according to findings from the phase 3 COSMIC-313 trial (NCT03937219) presented at the 2023 Genitourinary Cancers Symposium.

The median 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.


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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