BELZUTIFAN TAB
Clinical Criteria Summary
Document 713
Exclusion Criteria
- Untreated and symptomatic central nervous system (CNS) metastases
- Unmanageable drug-drug interactions
- Moderate-Severe hepatic impairment (Total bilirubin > 1.5 X Upper Limit of Normal and any AST)
- Pregnancy
- Lactation
Inclusion Criteria
- Advanced renal cell carcinoma (RCC) following a PD-1 or PD-L1 inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI) as monotherapy or in combination for locally advanced or metastatic RCC
Care Setting, Performance Status & Documentation Requirements
- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Counseling & Contraception Requirements
- For females who can become pregnant and males with female partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 1 week after stopping treatment
Document 714
Indication & Diagnosis
- Von Hippel-Lindau (VHL) Disease, based on germline VHL alteration
Inclusion Criteria
- Associated renal cell carcinoma, central nervous system (CNS) hemangioblastoma, or pancreatic neuroendocrine tumor not requiring surgery
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Exclusion Criteria
- Immediate need for surgical intervention for tumor treatment
- No evidence of metastatic disease
- Pregnancy
- Lactation
Counseling & Safety Requirements
- For females who can become pregnant and male patients with female partners who can become pregnant: Counseling provided on potential risks vs benefits and the use of effective contraception during therapy and for 1 week after stopping treatment
Provider & Care Setting Requirements
- Care is provided by a VA/VA Community Care oncology provider
Document 724
Indications & Patient Population
- Adults with von Hippel Lindau (VHL) disease for associated renal cell carcinoma (RCC), CNS hemangioblastoma, or pancreatic neuroendocrine tumors not requiring immediate surgery
- Advanced Renal Cell Carcinoma following PD-1 or PD-L1 inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI)
- Locally advanced/metastatic clear cell RCC with prior treatment with a PD-1/L1 inhibitor and VEGF TKI alone or in combination (NMT 3 prior systemic therapies), with progression, KPS ≥70%
Dosing & Administration
- 120mg (3 x 40mg tablets) once daily with or without food
- Available as 40 mg film-coated tablets
Safety, Monitoring, & Adverse Events
- Boxed Warning: Embryo-fetal Toxicity
- Contraindications: None
- Other Warnings: Anemia (gr 3 in 7% in VHL and 29% in advanced RCC), Hypoxia, Embryo-Fetal Toxicity
- Top Adverse Events: VHL population (anemia, fatigue, headache, dizziness, nausea); Advanced RCC population (anemia, fatigue, musculoskeletal pain, edema, nausea)
Drug Interactions
- UGT2B17 inhibitors and CYP2C19 inhibitors-increased exposure of belzutifan
Clinical Pathways & Guideline Context
- NCCN guidelines: No preferred therapies for subsequent therapy; Belzutifan is one choice out of 5 for subsequent therapy if patient had prior PD-1/L-1 therapy (2A)
- If only VEGF-TKI prior therapy, use belzutifan under certain circumstances (2B)
- VA Oncology Clinical Pathways: Nothing specific to VHL treatment; recurrent clear cell RCC currently recommends either of 2 combination therapies and then single-agent cabozantinib
- Note on standard of care: Everolimus alone is not considered standard treatment in this pre-treated population. Combination therapy, cabozantinib, or tivozanib would have been better comparators.