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COSMIC-313 Trial Lead Breaks Down Treatment Intensification in RCC

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Dr. Laurence Albiges discusses triplet therapies, highlighting which patients with RCC may garner the most benefit with this treatment intensification.

The phase 3 COSMIC-313 trial evaluated Cabometyx (cabozantinib), Opdivo (nivolumab) and Yervoy (ipilimumab) versus placebo plus Opdivo and Yervoy in patients with previously untreated, intermediate- or poor-risk advanced renal cell carcinoma (RCC), confirming that the combination significantly improved progression-free survival compared with the placebo regimen.

Furthermore, the objective response rate was higher with the investigative combination versus placebo. However, grade 3 (severe) and 4 (serious, life-threatening or disabling) treatment-emergent side effects were more frequent in the investigative arm (81% versus 62%). Grade 5 (death) treatment-related side effects were observed in 1% of patients in each group. According to investigators, further analyses are ongoing.

Glossary:

Progression-free survival: a measure used in clinical trials to evaluate the effectiveness of cancer treatments.

Objective response rate: the percentage of patients who have a complete or partial response to a treatment within a specific time frame.

Dr. Laurence Albiges, a professor, medical oncologist and head of the Department of Oncology at Institut Gustave Roussy, in Villejuif, France, sat down for an interview with CURE at the 2025 ASCO Genitourinary Cancers Symposium. In it, she discusses the importance of targeted therapies for patients with renal cell carcinoma, as well as who may garner the most benefit with this intensification of treatment.

Transcript:

COSMIC-313 is an important trial, because it paved the way of triplet [treatment], and we learned many lessons from this trial. The first one is that going to triplet [therapy] will not be a one size fits all, because of the toxicity. The second is that we may not want to have a blinded trial so that we can be better at managing toxicity in those [patients receiving treatment with the] triplet. The third is that we need to define the patient population that may need this intensification.

Does that be used up front or as a rescue strategy, for instance? Triplet therapy, to me, is not yet a standard of care. From a patient perspective, we need to understand who are the patients that will require this intensification … because [some individuals] have very rapidly progressive disease or need both of the components. But this is still a work in progress, and there are other triplet trials that will come to maturity in the coming months or years.

Transcript has been edited for clarity and conciseness.

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