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Renal Cell Carcinoma and von Hippel–Lindau Disease: Focus on Belzutifan Treatment

By: Cordi Craig, MS
Posted: Friday, January 7, 2022

Renal cell carcinoma develops in about 70% of patients who have the rare autosomal-dominant hereditary disorder known as von Hippel–Lindau disease. The high rate of cancer development is attributed to inactivation of the von Hippel–Lindau (VHL) gene and the subsequent activation of the transcription factor hypoxia-inducible factor 2α (HIF-2α). According to a phase II, single-group trial published in The New England Journal of Medicine, the HIF-2α inhibitor belzutifan may prove to be of benefit to patients with renal cell carcinoma associated with this hereditary disorder.

“The appropriate use of belzutifan in patients with von Hippel–Lindau disease remains to be determined,” Ramaprasad Srinivasan, MD, PhD, of the National Cancer Institute, Bethesda, Maryland, and colleagues stated. “However, data from the current trial suggest that belzutifan might serve as an alternative treatment or a complement to surgical treatment in these patients.”

The research team investigated the safety and efficacy of belzutifan in 61 patients with von Hippel–Lindau disease and at least one renal cell carcinoma tumor (≥ 10 mm). Patients were enrolled across 11 medical centers in the United States, Denmark, France, and the United Kingdom from May 2018 to March 2019. Most patients (n = 59; 97%) underwent at least one previous tumor reduction procedure such as partial nephrectomy, craniotomy, or cryoablation.

After a median follow-up of 21.8 months, nearly half of the patients with renal cell carcinoma (49%) achieved an objective response. Responses were also reported among patients with pancreatic lesions (77%) and central nervous system hemangioblastomas (30%). All 12 patients with baseline retinal hemangioblastomas showed improvement.

Adverse events were primarily grade 1 or 2. The most reported adverse events included anemia (90%) and fatigue (66%). Overall, seven patients discontinued treatment due to treatment-related adverse events (n = 1), disease progression (n = 1), patient death (n = 1), and voluntary discontinuation (n = 4).

Disclosure: For full disclosures of the study authors, visit

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