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New drug doubles progression-free time in brain cancer

Brain scan, CT brain image
CT scan of low grade glioma of the left parietal lobe. – Image credit Mikhail Kalinin via Wikipedia

CANCER DIGEST – June 17, 2023 – Brain cancer patients who had surgery and were given the drug vorasidenib doubled the time before the cancer progressed compared to patients who only underwent surgery, a new clinical trial shows. The trial results were published in the June 4, 2023 New England Journal of Medicine.

In the first clinical trial to analyze a targeted therapy drug specifically developed to treat brain cancer, 331 patients with grade 2 glioma that had recurred were randomly divided into two groups. Of these patients, 168 received the drug vorasidenib after surgery and 163 received a placebo. The vorasidenib group survived without their cancer worsening for 27.7 months, significantly longer than the 11.1 months of the comparison group.

In the vorasidenib group 85.6 percent went for 18 months before their next treatment and 83.4 percent went 24 months before another treatment. The disease progressed in 28 percent of people receiving the drug compared to 54 percent of those who did not. Thirty months after the start of the study 72 percent of patients in the vorasidenib group were still taking the drug and their disease had not progressed.

The type of glioma treated had mutations in two genes that tend to affect younger patients as early as their 30s. The current treatment involves a combination of surgery when possible, radiation and chemotherapy, which have serious side effects in terms of cognitive function. The new drug had fewer and milder side effects.

“We’re always concerned about the delayed effects of radiation,” said co-senior author Dr. Timothy Cloughesy of UCLA in a press release. “Having the ability to hold off on getting radiation therapy to the brain with an effective therapy is really critical and very meaningful to this population of patients.”

Vorasidenib is classified as a dual inhibitor of mutant genes IDH1 and IDH2, which are thought to be responsible for the formation of IDH-mutant glioma tumors. These tumors can often cause headaches, nausea, speech or balance problems, difficulty swallowing and double vision, according to the National Brain Tumor Society.

One of the biggest challenges in treating brain cancers is getting through the blood-brain barrier, which has limited the effectiveness of many types of chemotherapies and targeted therapies. Vorasidenib is a brain-penetrant inhibitor, meaning it has the ability to cross the blood-brain barrier.

With the demonstrated benefit of the drug, patients in the placebo group were allowed to switch to vorasidenib.

“This is the first targeted treatment that shows unequivocal efficacy in this population and is precedent-setting for this disease,” Cloughesy said.

Sources: UCLA Jonsson Comprehensive Cancer Center press release, New England Journal of Medicine, and the National Brain Tumor Society


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