“Hats off to the investigators for the first comparison of triplet to doublet in advanced renal cell carcinoma. This is also the first results using a contemporary control group. The study met its primary endpoint,” said Sumanta K. Pal, MD, FASCO, Co-Director of the Kidney Cancer Program, City of Hope, Duarte, California, during his discussion of the COSMIC-313 trial.

Sumanta K. Pal, MD, FASCO

“Then the elephant in the room is that we haven’t seen the overall survival results. If the study meets the prespecified overall survival endpoint, we will see the triplet regimen utilized in a broader array of patients. However, we will need to attend to toxicity and quality of life,” Dr. Pal stated. In addition, he added, “if the study doesn’t meet the primary endpoint, I am optimistic we can identify a subset that benefits from this triplet therapy.”

Dr. Pal continued: “The improved progression-free survival in the intermediate-risk group runs counter to what I expected. This might be explained by the type of patients who enrolled in the trial. When I solicited opinions from Twitter, most said, ‘those with more aggressive disease,’” Dr. Pal noted.

“Does toxicity stand in the way of treatment? The takeaway is that grades 3 and 4 toxicities were substantially higher with the triplet, especially elevations in liver transaminases. Other studies will assess triplet therapy in this setting. An open-label trial design may allow us to discern the source of toxicity,” he suggested.

“As we add more therapies, we add more toxicity. We need to determine how to select patients for a more aggressive regimen and use a risk-adapted approach. Biomarker studies are needed. Another way forward is to use therapies without overlapping toxicities,” Dr. Pal stated. 

DISCLOSURE: Dr. Pal has received travel support from Ipsen and CRISPR Therapeutics.