Belzutifan for Ocular Tumors in Patients with von Hippel-Lindau Disease.

Background: Belzutifan is an orally administered small molecule inhibitor of HIF-2-alpha that has been approved for use in von Hippel-Lindau (VHL)-associated renal cell carcinoma, central nervous system (CNS) hemangioblastomas, and pancreatic neuro-endocrine tumors. While use of the drug for treatment of VHL-associated retinal hemangioblastomas (RH) remains off-label, numerous case reports, case series, and a clinical trial sub-analysis have demonstrated excellent results in using the drug to control these tumors. Summary: We review the literature that has been published on the use of belzutifan for RH in patients with VHL. These studies have described good efficacy for treating RH and preventing the development of new ocular tumors. The efficacy for juxtapapillary and macular tumors that can be difficult to treat has been particularly promising. Dose reductions are commonly required due to side effects which most commonly include anemia and fatigue. Key Messages: While early reports are encouraging, the optimal dose of the drug for controlling RH along with the duration of therapy, role as a neoadjuvant, and ways to incorporate use of the drug into the treatment and screening paradigms for VHL-associated ocular disease are evolving.