When cancer cells spread from their original site to the brain, this is referred to as brain metastasis. Any cancer can spread to the brain, but the most common types are lung, breast, colon, kidney, and melanoma. Brain metastases can result in the formation of one or more tumors in the brain. Metastatic brain tumors put pressure on and alter the function of surrounding brain tissue as they grow. This results in signs and symptoms like headaches, personality changes, memory loss, and seizures.
A targeted drug has shown promising activity against brain metastases caused by kidney cancer, achieving a 50% response rate and paving the way for further research into the drug in this patient group, where the poor prognosis has created a significant unmet need.
Cabozantinib is a tyrosine kinase inhibitor that targets multiple targets in cancer cells. It has been approved for the treatment of advanced renal cell (kidney) cancer, but there has been very little testing in patients with brain metastases. Historically, these patients have been excluded from clinical trials due to concerns about their life expectancy and the tolerability of the intervention. According to senior author Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, cabozantinib can potentially pass through the blood-brain barrier to reach metastases, some of which shrank significantly.
We measured the dimension of the metastases in the brain and saw a response rate that was higher than what we usually expect, and there were some nice examples of metastases really shrinking. However, that some of the responses were not long-lasting, and the tumors became resistant after a few months.
Toni Choueiri
The drug was well tolerated in two groups of patients, totaling 88 people with kidney cancer brain metastases. Some patients received additional local treatment, such as surgery or radiation, while others did not. Patients in one cohort lived for a median of 15 months, while patients in the other cohort lived for a median of 16 months.
According to Choueiri, kidney cancer spreads to the brain in 2-10% of patients, causing significant morbidity and mortality; metastases are typically treated with surgery and/or radiation. Until now, systemic treatment with targeted drugs like sunitinib has been relatively ineffective, and immunotherapy drugs have also been ineffective. “Many drugs that work well outside the brain do not work well for brain metastases,” Choueiri observed.
A few isolated case reports of cabozantinib benefiting kidney cancer patients with brain metastases prompted the new trial. “Given the paucity of literature and the high clinical need, we sought to assess the activity and safety of cabozantinib in patients with brain metastases from renal cell cancer using an international multicenter collaboration,” the researchers explained.
“We measured the dimension of the metastases in the brain and saw a response rate that was higher than what we usually expect, and there were some nice examples of metastases really shrinking,” said Choueiri after treatment with cabozantinib. He cautioned, however, that some of the responses were not long-lasting, and the tumors became resistant after a few months.
The research was done in retrospect. A prospective phase II trial of cabozantinib is currently underway in France, according to Choueiri, “and hopefully this will be definitive.” While surgery and radiation are currently the gold standard for treating brain metastases in kidney cancer, Choueiri claims that these treatments don’t always work or can’t be used in certain areas of the brain. “It would be beneficial to have a systemic option for these patients,” he says.
The majority of patients with kidney cancer who have brain metastases also have metastatic spread to other organs. According to the findings of the new study, the response rate to cabozantinib treatment was roughly the same for these extracranial metastases as it was for brain metastases.
Surgery, radiation therapy, chemotherapy, immunotherapy, or a combination of treatments may be used to treat people whose cancer has spread to their brains. In some cases, other treatments may be advised. Treatment is frequently focused on reducing cancer-related pain and symptoms.
