“Spectacular” Trial Results Establish New Standard of Care for Advanced Kidney Cancer

Brian Rini, MD, Professor of Medicine and Leader of the GU Program at Cleveland Clinic Taussig Cancer Center, Ohio, discusses the pivotal results of the KEYNOTE-426 trial, which compared the use of axitinib plus pembrolizumab with sunitinib in treatment-naïve patients with advanced kidney cancer.

Transcript

This is Brian Rini, I'm a Professor of Medicine and Leader of the GU program at Cleveland Clinic Taussig Cancer Center.

Another large study, and probably the most important that was presented at the GU Symposium, was the KEYNOTE-426 study.

I was very involved with study, which was presented by Tom Powles from London. This was a study that looked at the combination of axitinib and pembrolizumab compared to sunitinib in previously untreated advanced kidney cancer.

Just a bit of background, 2 things—one is that these combinations of VEGF agents and immune-oncology agents have sort of taken over in the frontline treatment of kidney cancer. There was a phase 1 study of this combination that showed a high degree of activity, very long progression-free survival (PFS) and high response rate, as has been true with some other similar combinations. This was studied in a phase 3 setting, compared to what has been the historic standard of care of sunitinib monotherapy. What was seen was frankly nothing short of spectacular.

The overall survival favored axitinib plus pembrolizumab, and the hazard ratio was 0.53 which was the lowest hazard ratio that's ever been observed for survival in any phase 3 trial.

This benefit was seen across prognostic risk groups, and it was also seen regardless of PD-L1 expression, so very broad benefit to the general kidney cancer population, which will make these data applicable (once it receives approval) to most kidney cancer patients, if not all kidney cancer patients, that walk through the door.

There was also a significant PFS advantage. The PFS of the combination was 15 months, again the longest ever reported, and the response rate was nearly 60%, for the combination again, which is the highest ever report with a complete response rate of 6%. What is also impressive is these data are relatively immature; there's only a year of median follow-up, so to hit this striking survival signal early with the P value that was required is quite remarkable.

I have a feeling that some of the end points, such as response and complete response, etc., may improve over time. It also is reasonably well-tolerated with some of the expected side effects that you get from each class of agent.

I think these data are exceedingly important, they will establish new standard of care in this disease, and are now the standard upon which other regimens, including other similar regimens that have yet to be reported, will be compared.