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Treatments for people with metastatic kidney cancer have changed over the past several years, resulting in big improvements in patient outcomes and survival. However, unfortunately for most patients their cancer eventually gets worse over time despite treatment.
Studies looking at the genes of people with kidney cancer have shown mutations in a gene called the von Hippel-Lindau gene (VHL). This results in high levels of a protein called hypoxia-inducible factor, or HIF-2α in the blood of these patients. This causes changes in the cancer cells that make the tumour grow. A new medicine called belzutifan is a tablet that blocks the action of HIF-2α and, therefore, blocks cancer cell growth.
Belzutifan has been approved in some countries for the treatment of people with VHL disease who develop tumours in the kidney, brain and spinal cord, or pancreas. Belzutifan has also been shown to be effective for the treatment of advanced kidney cancer.
At the ESMO Congress 2023 the results from 3 clinical trials with belzutifan for the treatment of advanced kidney cancer were presented.
Taking belzutifan in combination with cabozantinib shows promise for the treatment of advanced kidney cancer (the LITESPARK-003 study)
Early results from the LITESPARK-003 study showed promising results for belzutifan together with cabozantinib as the first anti-cancer medication (a first-line treatment) for patients with advanced kidney cancer and as a treatment for patients who had already been treated with immunotherapy. Updated results from this study were presented at the ESMO Congress.
LITESPARK-003 is a phase 2 study looking at the safety and effectiveness of belzutifan in combination with cabozantinib, a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) tablet, in patients with clear cell kidney cancer. The patients were assessed in two groups: Group 1 were patients who had not been treated with anti-cancer medication; group 2 had already been treated with two or less immunotherapies.
There were 50 patients in group 1. After an average follow-up time of 2 years, 6 in 10 patients responded to treatment and their cancer got smaller. One patient had a complete response to treatment and their cancer disappeared. Just over half of the patients had a partial response to treatment. In over a third of patients their cancer was stable. Nearly 6 in 10 patients had a response to treatment that lasted 2 years or more. The average time to when the treatment stopped working and the cancer started growing again (progression-free survival) was just over 2 and a half years for patients in group 1. The average overall survival time could not be measured during the follow-up time.
Nearly half of the patients (46%) in group 1 had serious or life-threatening side effects. There were no deaths in this group of patients.
The study is ongoing for the patients in group 1 (untreated patients) to collect more information about survival.
There were 52 patients in group 2. After an average follow-up time of over 3 years, a third of patients responded to treatment with belzutifan plus cabozantinib and their cancer got smaller. Two patients had a complete response to treatment and their cancer disappeared. More than a quarter of the patients had a partial response to treatment. Six in 10 patients had stable disease. More than half of the patients had a response to treatment that lasted more than 2 years. The average time to when the treatment stopped working and the cancer started growing again (progression-free survival) was just over a year for patients in group 2. Overall survival time was more than 2 years.
Nearly two thirds of patients from group 2 had a serious or life-threatening side effect. Unfortunately, one patient died due to respiratory failure, which was because of the combination treatment.
The results from the LITESPARK-003 study showed that belzutifan has promise as an effective treatment for patients with advanced kidney cancer when given together with cabozantinib, both as a first anti-cancer medication and for patients that have already been treated with immunotherapy.
Belzutifan compared to everolimus in patients with previously treated advanced clear cell kidney cancer (the LITESPARK-005 study)
There were 746 patients with advanced kidney cancer in the phase 3 LITESPARK-005 study. They were randomised to be treated with either belzutifan or everolimus, an mTOR inhibitor tablet. Patients had already been treated with between 1-3 courses of immunotherapy or VEGFR TKI. Patients were followed-up for over 2 years.
The time to when the treatment stopped working and the cancer started growing again (progression-free survival) and the response to treatment were better with belzutifan compared to everolimus. Overall survival time was longer for patients treated with belzutifan, although not statistically significant (21 months compared to 18 months, respectively). 13 patients (3.5%) had a complete response to treatment with belzutifan and their cancer disappeared. There were no complete responses with everolimus. More patients did not have growth of their cancer at 1.5 years with belzutifan compared to everolimus (22.5% compared to 9.0%, respectively).
Nearly three times as many patients stopped treatment because of side effects to everolimus compared to belzutifan. The number of serious and life-threatening side effects were similar for both treatments.
For patients with advanced kidney cancer who had already been treated with immunotherapy or targeted therapy, belzutifan increased the time to when the cancer started growing again compared to everolimus. Also, more patients responded to treatment with belzutifan compared to everolimus. Belzutifan was relatively well tolerated, and no new side effects were reported.
Safety and effectiveness of two doses of belzutifan in patients with advanced kidney cancer (the LITESPARK-013 study)
In a phase 1 study of belzutifan, the maximum dose tolerated by patients for the treatment of kidney cancer was not found. The phase 2 LITESPARK-013 study looked at using a higher dose of belzutifan to see if it improved the effectiveness of the anti-cancer medication while making sure the medicine was tolerated by patients.
There were 154 patients in the study with advanced kidney cancer. Patients had been treated with up to 3 anti-cancer medications, including immunotherapy. Patients were randomly put into two treatment groups: 120 mg tablets of belzutifan every day or 200 mg tablets of belzutifan every day. Patients were followed-up for 20 months.
The response to treatment and progression-free survival were similar for both the 120 mg and 200 mg tablets of belzutifan. The side effects were similar for each tablet. No new side effects were reported.
The 120 mg tablet of belzutifan had similar anti-cancer effectiveness to the 200 mg tablet in patients with advanced kidney cancer. Belzutifan was relatively well tolerated, and no new side effects were reported. This study shows that the 120 mg tablet taken every day is the preferred dose of belzutifan for treating advanced kidney cancer.
