Does COSMIC-313 Make the Case for Triplet Therapy in RCC?

Yousef Zakharia, MD, a medical oncologist and clinical associate professor of internal medicine-hematology, oncology, and blood and marrow transplantation in the Department of Internal Medicine at University of Iowa Hospitals & Clinics, discusses the COSMIC-313 study and its implications to date.

According to Zakharia, interim analysis data from COSMIC-313 alone are not sufficient to support oncologists choosing triplet therapy over doublet therapy for patients with RCC. The study investigated the immune-oncology (IO) and tyrosine kinase inhibitor (TKI) combination of nivolumab (Opdivo) and ipilimumab (Yervoy) or ipi/nivo plus cabozantinib (Cabometyx) vs ipi/nivo alone, and it showed positive results.

The use of doublet IO/TKI therapy, however, can be rationalized. In the CheckMAte-214 clinical trial, ipi/nivo demonstrated a favorable overall survival when compared with sunitinib (Sutent; HR, 0.46;95% CI 0.29-0.71; P =.0004; as well as an improvement in progression-free survival (; HR, 0.50;95% CI 0.32-0.80; P =.0036).

In addition to interim results being insufficient to make the case for using triplet therapy, Zakharia says the adverse events associated with the triplet combination are concerning. More information around how to manage the toxicities.

Transcript:

0:08 | The study was positive, the CSOMIC 313 certainly was a positive study on a first interim analysis, if you will. And this was comparing the triplet of nivolumab plus ipilimumab and cabozantinib versus ipi/nivo with a primary endpoint of PFS. The triplet indeed did improve PFS in the intention-to-treat population [and] more so was in the intermediate-risk patient population per the IMDC risk stratification.

0:40 | The downside, I would argue of that regime, I think is the side effects profile that is associated with it, and the lack of overall survival data. Certainly, we will need longer follow up to see how the overall survival is going to pan out, and the as I mentioned the toxicity profile mainly with the hepatitis or the liver toxicity, and the diarrhea are discouraging signals if you will.