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Kidney cancers often have mutations in a gene called the von Hippel-Lindau (VHL) gene. This results in high levels of a protein called hypoxia-inducible factor, or HIF-2α. HIF-2α causes several changes in the cancer cells that cause the tumour to grow. Belzutifan is a HIF-2α inhibitor, which blocks the action of HIF-2α.
The safety and efficacy of belzutifan in combination with cabozantinib, a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI), was assessed in patients with clear cell kidney cancer who had been previously treated with immunotherapy (group 2) in a phase 2 clinical trial. (Group 1 included patients who were previously untreated, see below). Just over half of the patients (54%) had been treated with one course of immunotherapy, while the remainder (46%) had ben treated with two courses of immunotherapy.
Overall, there were 52 patients in group 2. After an average of 2 years follow-up, nearly a third of patients responded to the belzutifan plus cabozantinib combination and their cancer got smaller. One patient had a complete response to treatment and the cancer disappeared.
High blood pressure (hypertension) was the most common serious or life-threatening side effect, which occurred in just over a quarter of patients. Unfortunately, one patient died due to respiratory failure. The researchers considered this to be as a result of the combination treatment.
In this study belzutifan showed promising anti-cancer activity when given with cabozantinib in patients with metastatic clear cell kidney cancer that had been previously treated. The results suggest that the combination might fill an unmet need and provides a reason to study a VEGF TKI plus HIF-2α inhibitor combination further.
Belzutifan/cabozantinib as a first-line treatment
Results from group 1 of the clinical trial showed that the belzutifan plus cabozantinib combination is also promising as a first-line treatment for patients with locally advanced or metastatic clear cell kidney cancer.
This group included 35 patients. After an average follow-up time of 14 months, 57% of patients responded to treatment. Two patients had a complete response to treatment and just over half of the patients had a partial response to treatment. In over a third of patients (37%) their cancer was stable. Overall, the cancer was controlled in 94% of patients.
Over a third of patients (37%) had serious side effects. There were no life-threatening side effects or deaths in this group of patients.
This clinical trial is ongoing for previously untreated patients to see if these survival outcomes continue with a longer follow-up.
