Belzutifan elicits responses in patients with renal cell carcinoma (RCC) associated with von Hippel-Lindau (VHL) disease, according to research published in The New England Journal of Medicine.

Belzutifan demonstrated activity against both RCC and non-RCC neoplasms associated with VHL disease in a phase 2 trial ( identifier: NCT03401788).

The trial enrolled 61 patients with VHL-associated RCC treated at 11 centers in the United States, United Kingdom, Denmark, and France. The patients’ median age was 41 years (range, 19-66 years), and 52% were men.

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All patients had RCC and pancreatic lesions. Fifty patients (82%) also had central nervous system (CNS) hemangioblastomas, and 12 patients (20%) had retinal hemangioblastomas.

The patients received belzutifan at 120 mg daily. The median treatment duration was 21.7 months, and 54 patients (89%) were still on treatment at the data cutoff. The median follow-up was 21.8 months.

In renal tumors, the objective response rate was 49%, with all 30 responders achieving a partial response. Another 30 patients (49%) had a best response of stable disease. The median duration of response was not reached.

In pancreatic lesions, 47 patients (77%) responded, including 6 who had a complete response. In CNS hemangioblastomas, 15 patients (30%) responded, including 3 with a complete response. All 16 evaluable eyes in patients with retinal hemangioblastomas showed improvement.

All patients had at least 1 treatment-related adverse event (AE). Nine patients (15%) had grade 3 treatment-related AEs, and there were no grade 4 or 5 AEs related to treatment. Twenty-six patients (43%) had treatment interruptions due to AEs, 9 patients (15%) had dose reductions due to AEs, and 1 patient discontinued treatment due to a related AE.

“We found that belzutifan has mainly low-grade side effects that affect most patients who take it and has shown activity in patients with renal cell carcinoma associated with VHL disease, pancreatic neuroendocrine tumors, and hemangioblastomas by targeting the underlying pathophysiology of the disease,” the researchers concluded.

Disclosures: This study was supported by Merck Sharp and Dohme.  Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Jonasch E, Donskov F, Iliopoulos O, et al. Belzutifan for renal cell carcinoma in von Hippel–Lindau disease. N Engl J Med. Published online November 25, 2021. doi:10.1056/NEJMoa2103425