Belzutifan is a tablet that works in a different way (it blocks a protein called HIF-2α, which is overactive in clear-cell kidney cancer). In patients whose disease had progressed after immunotherapy and anti-angiogenic drugs, belzutifan shrank the tumour in more patients than everolimus (about 22 versus 4 out of every 100), and more patients were free of progression after 18 months; however, a longer life was not statistically proven in this analysis. Anaemia is one of its common side effects.
Advanced RCC with a clear-cell component after a PD-1 or PD-L1 inhibitor and a VEGF-TKI
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Belzutifan | 120 mg once daily | Oral, with or without food; do not crush tablets | Daily, continuously |
Per the FDA label and the trial. Anaemia is very common: haemoglobin <8 g/dL or transfusion needed: withhold. Oxygen saturation <88% at rest: withhold, then resume at a reduced dose or discontinue.
On the page “Kidney cancer” · Regimens for later lines and immunotherapy-free treatment
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Belzutifan 120 mg orally once daily (with or without food) until disease progression or unacceptable toxicity. According to the FDA label, dose reduction to 80 and then 40 mg; temporary interruption for haemoglobin below 8 g/dL or decreased oxygen saturation.
Everolimus 10 mg orally once daily until disease progression or unacceptable toxicity.
Source of the regimen details: Published abstract (NEJM 2024), ClinicalTrials.gov NCT04195750 and the FDA label (WELIREG)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Patients with advanced clear-cell renal cell carcinoma (unresectable, locally advanced or metastatic) that had progressed after an immune checkpoint inhibitor (PD-1/PD-L1) and anti-angiogenic therapy (VEGF-TKI), given sequentially or in combination, and who had received up to 3 prior systemic regimens for advanced disease (ClinicalTrials.gov).
Dual primary endpoints: progression-free survival and overall survival. Key secondary endpoint: objective response (confirmed complete or partial response).
Grade 3 or higher adverse events of any cause occurred in 61.8% of the belzutifan group (grade 5 in 3.5%) and 62.5% of the everolimus group (grade 5 in 5.3%). Discontinuation due to adverse events was less frequent with belzutifan (5.9% versus 14.7%). According to the FDA announcement, the most common adverse reactions to belzutifan (incidence at least 25%) included decreased haemoglobin, fatigue, musculoskeletal pain, increased creatinine, decreased lymphocytes, increased liver enzymes (ALT and AST), decreased sodium and increased potassium. According to the FDA label, in this trial decreased haemoglobin occurred in 88% of belzutifan patients (grade 3 in 29%) and hypoxia in 15% (grade 3 in 10%).
Based on this trial, on 14 December 2023 the FDA approved belzutifan (Welireg) for patients with advanced renal cell carcinoma after a PD-1 or PD-L1 inhibitor and a VEGF-TKI (recommended dose 120 mg orally once daily). Belzutifan had previously also been approved for tumours associated with von Hippel-Lindau (VHL) disease. The EAU 2022 and NCCN 3.2022 guidelines shown on this page were written before these results were published.
Open-label design; median progression-free survival was identical in the two groups and the curves were non-proportional; superiority in overall survival was not shown at the second interim analysis; the comparator (everolimus) is an option with relatively limited efficacy.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
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