The addition of Cabometyx to the current standard-of-care frontline regimen of Opdivo plus Yervoy improved progression-free survival outcomes in patients with advanced kidney cancer.
Adding Cabometyx (cabozantinib) to the immunotherapy duo Opdivo (nivolumab) and Yervoy (ipilimumab) lengthened the time from treatment to worsening disease — known as progression-free survival — in patients with previously untreated advanced kidney cancer, according to findings from the phase 3 COSMIC-313 clinical trial.
Dr. Toni Choueiri, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute in Boston, presented the data at the 2022 European Society of Medical Oncology Congress.
The risk for disease progression or worsening was reduced by 27% with the addition of Cabometyx (276 patients), compared with adding a placebo (274 patients), to Opdivo plus Yervoy, which is the current standard of care for this patient population.
Average progression-free survival for the three-drug therapy was not reached at the time of data collection, meaning that patients still did not experience disease progression. For the placebo plus immunotherapy group, average progression-free survival was 11.3 months. At the 12-month mark, 57% of patients and 49% of patients in the Cabometyx and placebo groups, respectively, did not experience disease progression.
Moreover, the objective response rate, which measures how much of the tumors shrunk, with the addition of Cabometyx was 43%, compared with 36% with placebo.
When stratified by intermediate (75%) and poor risk (25%), the progression-free survival benefit was greater with Cabometyx plus Opdivo and Yervoy in the intermediate-risk group. In the intermediate-risk subgroup, median progression-free survival was not reached with the triplet, compared with 11.4 months with placebo, reducing the risk for disease progression by 37%.
The objective response rate with Cabometyx compared to placebo in those with intermediate-risk disease were 45% and 35%, respectively.
In those with poor-risk disease, the median progression-free survival was 9.5 months with Cabometyx plus Opdivo and Yervoy, versus 11.2 months with placebo. The objective response rate with Cabometyx and placebo were 37% and 38%, respectively.
Choueiri noted that the safety profile of Cabometyx plus Opdivo and Yervoy was generally manageable and consistent with the profiles of each respective therapy component. However, side effects, which included elevated liver transaminases (which could indicate inflammation or other issues with the liver), diarrhea and skin toxicity, occurred more frequently with the triplet regimen.
Overall, severe side effects occurred in 73% and 41% of patients in the Cabometyx and placebo groups, respectively. Three patients (1%) in each treatment group had fatal side effects, while 12% and 5% of patients, respectively, discontinued treatment due to side effects.
“COSMIC-313 is the first study that reported successful treatment intensification by the use of triplet therapy in (metastatic kidney cancer): The study team and participants should be congratulated for study conduct,” Dr. Viktor Grünwald, of the University Hospital Essen and West-German Cancer Center in Essen, Germany, said in a press release commenting on the data. “The addition of (Cabometyx) to (Yervoy) plus (Opdivo) improved the weak spot of the (Yervoy/Opdivo) doublet, which is early progression. However, treatment intensification is rarely seen without additional risks. Patients experienced the benefit of superior disease control, but also additional toxicities, treatment pauses and discontinuations.”
To conclude, Choueiri noted that follow-up for overall survival is ongoing.
“Despite in COSMIC-313 the triplet (Yervoy, Opdivo and Cabometyx) yielded superior progression-free survival when compared to the doublet (Yervoy plus Opdivo), no overall survival data were reported,” Grünwald added. “The triplet may compete in the clinical landscape with recommended life-prolonging immune doublets, but mature overall survival data is needed to become a novel standard of care.”
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