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Kidney cancers often have mutations in a gene called the von Hippel-Lindau (VHL) in high levels of a protein called -inducible factor, or HIF-2α. HIF-2α causes several changes in the 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 kidney cancer who had been previously treated with (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 , while the remainder (46%) had ben treated with two courses of .was assessed in patients with
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-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.activity when given with in patients with metastatic
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.