An international phase 3 study has shown that combining the HIF-2α inhibitor belzutifan with lenvatinib delays disease progression in patients with metastatic clear cell renal cell carcinoma who were previously treated with immunotherapy. The LITESPARK-011 trial was conducted at 184 centers in 24 countries and has been published in The Lancet.
Patients receiving the combination treatment had a median progression-free survival of 14.8 months, compared with 10.7 months for patients treated with cabozantinib. An improvement in overall survival of approximately seven months was also observed, although these results are still based on an interim analysis.
A new target in kidney cancer
Belzutifan inhibits HIF-2α, a protein that plays an important role in clear cell renal cell carcinoma. It was combined with lenvatinib, a targeted treatment that inhibits angiogenesis. “HIF-2α is a new target in the treatment of kidney cancer,” says internist-oncologist Britt Suelmann of UMC Utrecht. “In addition to immunotherapy and existing targeted therapies, we now have an extra target. This increases the number of treatment options for patients.”
“The survival data are not yet fully mature. “A significant proportion of patients are still using the treatment. It is therefore quite possible that the difference in survival will increase even further in later analyses,” adds Suelmann.
Belzutifan was also well tolerated compared with other drugs used to treat kidney cancer. “We see anemia as the most common side effect, but it is easy to manage,” says medical oncologist John Haanen of the NKI.
Strong Dutch contribution
Amphia, UMC Utrecht, and the Netherlands Cancer Institute contributed substantially to patient enrollment in the study. Close collaboration within national and regional kidney cancer networks helped hospitals identify and refer eligible patients to participating centers.
“In recent years, we have increasingly organized kidney cancer care regionally,” explains internist-oncologist Hans Westgeest of Amphia. “As a result, hospitals know how to find each other easily, and patients eligible for a study can be referred quickly.”
“The alternatives outside of a study setting are less effective than both treatment arms within the study. Patients were therefore eager to participate in the LITESPARK-011 study,” explains Haanen. “We hope that, based on these results, this treatment will become available as a new option for our patients in the near future.”