Treating Renal Cell Carcinoma with Belzutifan, a HIF-2α Inhibitor
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on October 2nd, 2024
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Ninety percent of renal cell carcinoma cases involve mutations in the VHL gene, which leads to upregulation of the HIF pathway, driving tumorigenesis, angiogenesis, and metastasis. Belzutifan has the potential to disrupt this pathway by binding to the HIF2α transcription factor and inhibiting its dimerization. In light of this, Merck sponsored a study to assess the efficacy of belzutifan in treating renal cell carcinoma.
The phase 3 clinical trial included 746 participants diagnosed with stage IV clear-cell renal-cell carcinoma, based on the American Joint Committee on Cancer staging manual. The study enrolled patients with advanced disease, defined by a Karnofsky score greater than 70. Participants were randomly assigned to receive either 120 mg of belzutifan daily or the current standard treatment, the mTORC inhibitor everolimus, at a daily dose of 10 mg. After 18 months, researchers found that belzutifan was more effective than everolimus in delaying disease progression and reducing mortality, with 24% of the belzutifan group staying alive without disease progression compared to 8.3% in the everolimus group. Additionally, over 20% of patients treated with belzutifan experienced tumor shrinkage or complete remission, compared to just 3.5% in the everolimus group. The researchers advised that healthcare providers should monitor for anemia and hypoxia in patients treated with belzutifan and consider blood transfusions when necessary.
The phase 3 clinical trial included 746 participants diagnosed with stage IV clear-cell renal-cell carcinoma, based on the American Joint Committee on Cancer staging manual. The study enrolled patients with advanced disease, defined by a Karnofsky score greater than 70. Participants were randomly assigned to receive either 120 mg of belzutifan daily or the current standard treatment, the mTORC inhibitor everolimus, at a daily dose of 10 mg. After 18 months, researchers found that belzutifan was more effective than everolimus in delaying disease progression and reducing mortality, with 24% of the belzutifan group staying alive without disease progression compared to 8.3% in the everolimus group. Additionally, over 20% of patients treated with belzutifan experienced tumor shrinkage or complete remission, compared to just 3.5% in the everolimus group. The researchers advised that healthcare providers should monitor for anemia and hypoxia in patients treated with belzutifan and consider blood transfusions when necessary.