A new combination treatment for patients with metastatic kidney cancer has shown positive results in the international phase 3 study LITESPARK-011. Dutch centers made a significant contribution to the study: Amphia Hospital, UMC Utrecht, and the Netherlands Cancer Institute (NCI) enrolled a relatively large number of patients. The results have been published in The Lancet.
The treatment of metastatic kidney cancer has improved significantly in recent years due to advances in immunotherapy and targeted therapies. As a result, patients with metastatic kidney cancer live considerably longer on average than fifteen years ago. Nevertheless, there remains a need for new treatments.
Britt Suelmann
“We have an increasing number of treatment options available, but patients often experience renewed disease progression over time,” says internist-oncologist Britt Suelmann (UMC Utrecht). “That is why it is important that we continue to search for new targets for therapies.”
The LITESPARK-011 study investigates a new treatment strategy combining lenvatinib, a tyrosine kinase inhibitor that inhibits angiogenesis, with belzutifan, an inhibitor of the protein HIF-2α. “HIF-2α is a new target in the treatment of kidney cancer,” explains Britt. “In addition to immunotherapy and existing targeted therapies, we now have an extra target. This increases the number of treatment options for patients.”
Longer progression-free survival
In the study, this combination was compared with cabozantinib, an existing and widely used targeted treatment. This large international study took place in 184 centers in 24 countries and focused on patients with metastatic clear cell renal cell carcinoma (ccRCC) who had previously received immunotherapy.
Progression-free survival (PFS) was 14.8 months in patients receiving the combination treatment, compared with 10.7 months in patients receiving cabozantinib. An improvement in overall survival (OS) of approximately 7 months was also observed, although these results are based on an interim analysis.
“The survival data are not yet fully mature,” says Britt. “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.”
Importantly for these patients, the HIF-2α inhibitor belzutifan is very well tolerated, particularly compared with other drugs for kidney cancer. “We see anemia as the most common side effect, but it is easy to manage,” says internist-oncologist John Haanen (NCI).
Hans Westgeest
Strong collaboration
According to internist-oncologist Hans Westgeest (Amphia), the high patient enrollment in the Netherlands is the result of a well-organized care network. “In recent years, we have increasingly organized kidney cancer care regionally,” explains Hans. “As a result, hospitals are well connected, and patients eligible for a study can be referred quickly.”
Moreover, Dutch hospitals collaborate closely in the field of kidney cancer within the Dutch Renal Cell Carcinoma Group (DRCG) and regional oncology networks such as ONCONOVO+, ONCOMID, and EMBRAZE. Within these collaborations, patients are discussed and, if necessary, referred to centers where clinical trials are underway. When the LITESPARK-011 study started in 2021, that network proved to be an important factor in patient enrollment.
“Many patients who participated in the study at our center actually came from other hospitals in the region. Thanks to that collaboration, we were able to give many patients access to a new treatment”, Hans explains. Amphia ultimately enrolled nineteen patients, far more than initially expected. This was the highest number worldwide.
The high inclusion rate is also partly linked to the limited treatment options in the Netherlands for patients with metastatic kidney cancer who do not respond, or no longer respond, to previous immunotherapy.
“The treatment options outside a study setting are less effective than both treatment arms in this study. Patients were therefore eager to participate in the LITESPARK-011 study,” says John. “We hope that, based on these results, this treatment will become available as a new option for our patients in the near future.”
The Netherlands as a strong clinical research partner
According to Hans, the study also shows that the Netherlands remains an attractive country for international clinical research. “It is sometimes thought that the Netherlands has become less attractive for clinical trials, for example due to stricter reimbursement requirements,” says Hans.
“This study proves that we have an excellent infrastructure for clinical research and that we are a strong international partner. And naturally, we are all very proud of that.”
