Targeted drug shows promising activity in kidney cancer patients with brain metastases
A targeted drug has shown promising activity against brain metastases resulting from kidney cancer, achieving a response rate of 50 percent, and supporting further studies of the drug in this group of patients whose poor prognosis has created a significant unmet need.
The drug, cabozantinib, is a tyrosine kinase inhibitor that attacks multiple targets in cancer cells. It has been approved to treat advanced cancer of the kidney cells (kidneys), but has undergone very little testing in patients with brain metastases. Historically, these patients are generally excluded from clinical trials for the sake of life expectancy and tolerance to the intervention. The new report in JAMA Oncology suggests that cabozantinib can potentially cross the blood-brain barrier to reach metastases, some of which have dramatically decreased, said lead author Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute.
The drug was tolerated in two cohorts of patients, 88 people with brain metastases due to kidney cancer. Some patients also received local treatment with surgery or radiation therapy, while others did not. Patients in one cohort survived for a median of 15 months and 16 months in the other cohort.
Choueiri said kidney cancer spreads to the brain in 2-10% of patients, causing significant morbidity and mortality, and metastases are usually treated with surgery and / or radiation therapy. So far, systemic treatment with targeted drugs like sunitinib has been shown to be relatively ineffective, and immunotherapy drugs have not shown much benefit either. “A lot of drugs that work well outside the brain don’t work well for brain metastases,” Choueiri noted.
A few isolated case reports of cabozantinib in kidney cancer patients with brain metastases suggested a potential benefit, which prompted the new trial. “In view of the paucity of the literature and the high clinical needs, we sought to evaluate the activity and safety of cabozantinib in patients with brain metastases due to kidney cancer, taking advantage of a multi-center collaboration international, ”the researchers explained.
After treatment with cabozantinib, “we measured the size of the metastases in the brain and found a higher response rate than we usually expected, and there were some nice examples of metastases that really shrink,” said declared Choueiri. However, he warned, some of the responses were not lasting and the tumors became resistant after several months.
The study was retrospective. Choueiri said that a prospective phase II trial of cabozantinib is underway in France, “and I hope it will be definitive”.
While surgery and radiation therapy are currently the gold standard for treating brain metastases in kidney cancer, Choueiri said these modalities don’t always work or can’t be used in certain areas of the brain. “It would be nice to have a systemic option for these patients,” he said.
Most kidney cancer patients with brain metastases also have metastatic spread to other organs. The new study showed that the response rate with cabozantinib treatment was about the same for these extracranial metastases as it was for brain metastases.
The first two authors of the report are Laure Hirsch, MD, MsC, and Nieves Martinez Chanza, MD, PhD, both formerly of Dana-Farber and now at Cochin Hospital, University of Paris, France and at the Cancer Institute Jules Bordet, Brussels, Belgium, respectively.
Choueiri reports the personal expenses of Merck, Bristol Myers Squibb, Roche, EMDSerono, AstraZeneca, Exelixis, Pfizer and Eli Lilly during the conduct of the study; personal costs of the National Comprehensive Cancer Network, the National Cancer Institute Genitourinary Cancer Steering Committee, continuing medical education programs related to genitourinary oncology, and various national and international committees and programs outside of work submitted ; and support from the Dana-Farber / Harvard Cancer Center Kidney Cancer Specialized Program of Research Excellence (2P50CA101942-16) and the program (5P30CA006516-56), the Kohlberg Chair at Harvard Medical School, the Michael Brigham Fund and the Loker Pinard Funds for Kidney Cancer Research at Dana-Farber.
Dana-Farber Cancer Institute