Kidney cancers frequently have mutations in the von Hippel-Lindau (VHL) gene, resulting in high levels of a protein called hypoxia-inducible factor, or HIF-2α. This results in a number of changes in the cancer cells and their surrounding environment that favour tumour growth. The novel hypoxia-inducible factor 2α (HIF-2α) inhibitor, belzutifan (MK-6482), blocks the action of HIF-2α.
In a small phase 1/2 study, the safety and effectiveness of belzutifan was assessed in 55 patients who had taken several previous treatments for kidney cancer. Patients were followed for around 28 months.
Just over half of the patients had stable disease and in 80% of patients their cancer was controlled. For patients with favourable risk cancer, disease control rate was 92% and 76% for patients with intermediate or poor risk cancer. The average time to when the treatment stopped working and the cancer started growing again (progression-free survival) was 14.5 months, and more than half of the patients had progression-free survival of 12 months. A quarter of patients had shrinkage of their cancer. Sixty percent (60%) of patients stopped treatment due to progressive disease and 4% because of side effects.
The most common side effects were anaemia (76%), fatigue (71%), shortness of breath (49%), nausea (36%), cough (31%), and low blood oxygen (hypoxia, 31%). Two patients had serious, life-threatening side effects needing hospital treatment, and 4 patients died during the study. None of these side effects were related to treatment with belzutifan.
Belzutifan (MK-6482) is well tolerated and effective in patients with metastatic clear cell renal cell carcinoma (RCC). A phase III trial in patients with advanced RCC is underway, comparing belzutifan to everolimus. It is hoped the results from this trial will be available within the next year or two.