Salvage Therapy for Advanced Clear-Cell Renal Cancer

For patients with progressive, metastatic clear-cell renal cancer after treatment with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor receptor–tyrosine kinase inhibitors (VEGFR-TKIs), effective management options are limited. Alteration of the VHL gene occurs in the majority of clear-cell renal cancers and is associated with dysregulation of the hypoxia-inducible factor (HIF) pathway as a consequence of accumulation of HIF-2α. Belzutifan is a small-molecule inhibitor of HIF-2α with demonstrated activity in clear-cell renal cancer.

In this industry-sponsored, phase 3 trial, 746 patients with advanced clear-cell renal cancer previously treated with ICIs and antiangiogenic agents were randomized to receive either bel…