Analyzing Belzutifan Versus Everolimus for Patients With Advanced Renal Cell Carcinoma

Previous early-phase research demonstrated that the hypoxia-inducible factor 2α inhibitor, belzutifan, has shown clinical activity in patients with clear-cell renal cell carcinoma (ccRCC).

A phase 3 study from Toni K. Choueiri, MD, and colleagues published in The New England Journal of Medicine compared the effects of belzutifan and everolimus in patients with ccRCC.

In the multi-center, open-label trial, patients with ccRCC who had previously undergone treatment with immune checkpoint and antiangiogenic therapies received either belzutifan 120mg or everolimus 10mg once daily until reaching disease progression or unacceptable toxic effects.

The study’s primary endpoints were progression-free survival (PFS) and overall survival. The secondary endpoint was the incidence of object response.

Of the participants, 374 received belzutifan and 372 received everolimus. At a median follow-up period of 18.4 months, the median PFS was 5.6 months for both cohorts. In the belzutifan group, 24% of patients were alive, while 8.3% in the everolimus group were alive and progression-free.

A confirmed objective response occurred in 21.9% of patients in the belzutifan cohort (95% CI, 17.8-26.5) and 3.5% in the everolimus cohort (95% CI, 1.9-5.9; P<.001).

In the second interim analysis conducted at a median follow-up period of 25.7 months, the median overall survival was 21.4 months for patients in the belzutifan group and 18.1 months for those in the everolimus group.

Researchers reported that grade 3 or higher adverse events occurred in 61.8% of patients in the belzutifan cohort and 62.5% of patients in the everolimus cohort.

“Belzutifan showed a significant benefit over everolimus with respect to progression-free survival and objective response in participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies,” the researchers wrote. “Belzutifan was associated with no new safety signals.”