From the Guidelines
Welireg (belzutifan) is recommended for patients with von Hippel-Lindau disease who do not require immediate surgery, with a dosing regimen that should be individualized based on the patient's condition and tolerance. The management of renal cell carcinoma (RCC) in patients with von Hippel-Lindau (VHL) disease has evolved with the introduction of belzutifan, a hypoxia-inducible factor 2a transcription factor inhibitor 1.
Key Considerations
- VHL is a rare, autosomal dominant, hereditary disorder that often leads to the development of RCC, with approximately 70% of patients developing RCC during their lifetime 1.
- Historic approaches to managing RCC in VHL patients have relied on surgical or ablative methods, which can be challenging due to the propensity for multiple RCCs to develop, necessitating multiple procedures 1.
- A recent phase II trial investigated belzutifan in VHL-associated RCC, demonstrating an overall response rate of 64% and a reduction in the need for subsequent intervention, with the drug appearing to be well-tolerated 1.
Dosing and Administration
- While the exact dosing regimen is not specified in the provided evidence, the standard approach for similar conditions often involves oral administration, with considerations for dose adjustments based on adverse reactions.
- Patients should be monitored closely for signs of toxicity, and dose modifications should be made as necessary to balance efficacy with tolerability.
Mechanism of Action and Side Effects
- Belzutifan works by inhibiting hypoxia-inducible factor-2 alpha (HIF-2α), which is overactive in VHL disease due to the loss of the VHL protein, thereby reducing the formation of new blood vessels that feed tumors.
- Common side effects are likely to include anemia, fatigue, headache, and dizziness, among others, necessitating regular monitoring of hemoglobin levels and other parameters to ensure safe treatment.
From the Research
Recommended Use of Welireg (Belzutifan)
- Welireg (belzutifan) is approved for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery 2.
- The primary endpoint of the LITESPARK-004 study was the proportion of participants with an objective response in VHL disease-associated RCC per Response Evaluation Criteria in Solid Tumors, version 1.1, determined by an independent review committee 3.
Dosing of Welireg (Belzutifan)
- The recommended dose of belzutifan is 120 mg once daily, administered orally 3, 2, 4, 5.
- In the LITESPARK-004 study, participants received oral belzutifan 120 mg once daily, and the median study follow-up was 49.9 months 3.
Efficacy of Welireg (Belzutifan)
- The overall response rate (ORR) for VHL disease-associated RCC was 49% (95% CI, 36-62) 2, and 67% (95% CI, 54-79) of participants with RCC had an objective response in the LITESPARK-004 study 3.
- Responses were also observed in patients with CNS hemangioblastomas and pancreatic neuroendocrine tumors, with ORR of 63% (95% CI, 41-81) and 83% (95% CI, 52-98), respectively 2.
- In a single-institution retrospective experience, an ORR of 71% was observed in patients with CNS hemangioblastomas treated with belzutifan 5.
Safety of Welireg (Belzutifan)
- The most common adverse reactions reported in ≥20% of patients were anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea 2.
- In the LITESPARK-004 study, 13 grade 3 treatment-related adverse events occurred in 11 (18%) participants, and none of the participants had a grade 4 or 5 treatment-related adverse event 3.
- Belzutifan can render some hormonal contraceptives ineffective and can cause embryo-fetal harm during pregnancy 2.