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Belzutifan for Cancers Associated With von Hippel-Lindau Disease


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On August 13, 2021, belzutifan, a hypoxia-inducible factor inhibitor, was approved for treatment of adults with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma, central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors but do not require immediate surgery.1

Supporting Efficacy Data

Approval was based on findings in the ongoing Study 004 (ClinicalTrials.gov identifier NCT03401788). In this trial, 61 patients with VHL-associated renal cell carcinoma diagnosed based on a VHL germline alteration and at least one measurable solid tumor localized to the kidneys received oral belzutifan at 120 mg once daily until disease progression or unacceptable toxicity.

KEY POINTS

  • Belzutifan was approved for treatment of adults with von Hippel-Lindau disease who require therapy for associated renal cell carcinoma, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors but do not require immediate surgery.
  • The recommended belzutifan dosage is 120 mg orally once daily until disease progression or unacceptable toxicity.

Objective responses for patients with VHL-associated renal cell carcinoma on independent review committee assessment were observed in 30 patients (49%). After a minimum follow-up of 18 months, the median duration of response was not reached (range = 2.8+ to 22+ months), with 56% of responders having a response duration of at least 12 months. The median time to response was 8 months.

How It Is Used

The recommended belzutifan dosage is 120 mg orally once daily until disease progression or unacceptable toxicity. Recommended dose reductions for adverse reactions are to 80 and 40 mg/d. Product labeling provides instructions on dosage modification for anemia, hypoxia, and grade 3 or 4 adverse reactions.

Safety Profile

In Study 004, the most common adverse events of any grade (≥ 25%), including laboratory abnormalities, were decreased hemoglobin, anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea. The most common grade 3 or 4 laboratory abnormalities included decreased hemoglobin and increased glucose. Serious adverse events occurred in 15% of patients. Adverse events led to discontinuation of treatment in 3.3%. Belzutifan has a boxed warning for embryofetal toxicity. 

REFERENCE

1. Welireg (belzutifan) tablets prescribing information, Merck & Co., August 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215383s000lbl.pdf. Accessed September 7, 2021.


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