At the American Society of Clinical Oncology Genitourinary Cancers Conference (ASCO GU) last month, the results from the COSMIC-313 study were presented. This is the first study to combine cabozantinib with two immunotherapy medicines, nivolumab and ipilimumab. This combination of three medicines is compared with a combination of ipilimumab, nivolumab and placebo for the treatment of people with intermediate- or high-risk advanced kidney cancer.
855 patients were assessed in this phase 3 study. Patients were randomly assigned to receive either nivolumab and ipilimumab plus cabozantinib or nivolumab and ipilimumab plus placebo. The study is double-blind, meaning both the doctor and the patient do not know which treatment they are on. All patients had clear cell kidney cancer that was of intermediate- or high-risk.
Preliminary results from the clinical trial showed that adding cabozantinib to nivolumab plus ipilimumab significantly increased the time to when the treatment stopped working and the cancer started growing again (progression-free survival). Average progression-free survival was not reach for the triple combination, but for the ipilimumab plus nivolumab combination it was just over 11 months. Patients were assessed according to the severity (risk) of their cancer.
Overall, three quarters of the patients in the study had intermediate-risk cancer, and one quarter had poor-risk cancer. In the patients with intermediate-risk cancer, progression-free survival was improved with the triple combination, and response to treatment and control of the disease was higher compared with ipilimumab plus nivolumab (45% versus 35% and 88% versus 75%, respectively). For the patients with poor-risk disease, there was no difference in progression-free survival, but control of the disease was higher with the triple combination (81% versus 64%).
Serious and life-threatening side effects were reported by 74% of patients on the triple combination, and 42% on ipilimumab plus nivolumab in patients with intermediate-risk disease. In patients with poor-risk disease, serious and life-threatening side effects were reported in 67% of patients with poor-risk disease versus 38% for intermediate-risk disease. Side effects led to the treatment being stopped in 14% of patients on the triple combination versus 5% on the double combination for intermediate-risk patients and 5% versus 4% for poor-risk patients, respectively.
This subgroup analysis of the COSMIC-313 data suggests that the benefit of cabozantinib plus ipilimumab plus nivolumab is primarily for patients with intermediate-risk kidney cancer. However, the trial is continuing for the collection of overall survival data.