Adding Cabometyx to Immunotherapy Improves Kidney Cancer Outcomes

Patients with advanced renal cell carcinoma (RCC; the most common type of kidney cancer) of intermediate or poor risk tended to have better outcomes on a regimen consisting of Cabometyx (cabozantinib) plus the immunotherapy drugs, Opdivo (nivolumab) and Yervoy (ipilimumab) compared to placebo plus immunotherapy, according to updated findings from the phase 3 COSMIC-313 trial, which was presented at the 2023 ASCO GU Cancers Symposium.

At the 20.2-month follow-up point, patients given the three-drug treatment lived for an average of 16.9 months before their disease worsened (a statistic referred to as “progression-free survival), compared to 11.3 months in the group that received a placebo in lieu of Cabometyx.

A survival benefit was also observed in the intent-to-treat population, with median progression-free survival values of 15.3 months and 11.3 months in the experimental and placebo groups, respectively, after 17.7 months of median follow-up.

Among patients with intermediate-risk disease in the intent-to-treat population (which mirrors the real-word setting regarding issues like medication adherence), median progression-free survival was 17.9 months in the Cabometyx group, compared to 11.3 months in the placebo group.

For those with poor-risk disease the median progression-free survival was 9.5 months in the Cabometyx arm and 11.2 months in the placebo arm.

The objective response rate (percentage of people whose cancer shrinks or disappears from treatment) was 45% in the intermediate-risk subgroup among those treated with Cabometyx, compared with 36% among those treated with placebo. The disease control rate (DCR), meanwhile, was 88% and 74% in the experimental and placebo groups, respectively. The objective response rate 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 renal cell carcinoma according to International Metastatic RCC Database Consortium (IMDC) criteria. They were randomly assigned one of two groups: half of participants received Cabometyx at 40 mg by mouth daily or a matched placebo. Both treatment groups also received intravenous Opdivo and intravenous Yervoy every three weeks for 4 cycles, followed by Opdivo every four weeks for up to two years and Cabometyx 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 — which is the protein that the immunotherapy drugs target — less than 1%.

Nearly all patients experienced some kind of treatment-related side effect. The incidence of moderate to severe side effects was 74% across patients with intermediate-risk disease in the experimental group, compared with 42% across those in the placebo group. The corresponding values were 67% and 38%, respectively, across the poor-risk subgroup.

Treatment-related death 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 groups, respectively.

Total treatment discontinuation due to side effects occurred in 14% of those treated with Cabometyx, compared with 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.

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