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Key receivers
- A targeted therapy drug called voracitinib has shown positive results in slowing the growth of a certain type of glioma, a slow-growing but deadly brain cancer.
- In a study of 331 people, the drug was effective in prolonging the time before patients’ cancer progressed, with no side effects.
- New treatments for glioma are needed because current treatments, including chemotherapy and radiation therapy, can cause neurological deficits.
A new targeted therapy drug may extend the time people with other types of glioma stay on treatment without the cancer getting worse, scientists in an international study led by UCLA have found. The discovery suggests a new treatment option for people with slow-growing but deadly brain tumors.
The team found the drug voracitinib more than doubled progression-free survival in people with recurrent grade 2 glioma with IDH1 and IDH2 mutations. Compared to people who received a placebo, those who received voracitinib went 17 more months without their cancer getting worse and delayed the time they needed to start chemotherapy and radiation.
The results are published It was presented in the New England Journal of Medicine and today at the annual meeting of the American Society of Clinical Oncology in Chicago.
The type of glioma studied in the paper, recurrent 2 glioma with IDH1 and IDH2 mutations, affects young people, often in their 30s. The current standard of care, a combination of radiation and chemotherapy, can cause neurological deficits that make it difficult for patients to learn, remember new things, concentrate or make everyday decisions – all of which can be especially challenging for those with or with young families. In the early years of their professional life.
Dr. Timothy Clousey, Professor of Neuro-Oncology b David Geffen School of Medicine at UCLA And the study’s lead author says the availability of a treatment that allows patients to go longer between chemotherapy and radiation treatments could have a major impact.
“We are always concerned about the late effects of radiation,” said Clowsi, a member of the group. UCLA Johnson Comprehensive Cancer Center. “Having radiation therapy to the brain as an effective treatment is very important and beneficial for this patient population.”
Voracitinib is classified as a dual inhibitor of mutant IDH1/2, meaning it prevents the formation and accumulation of the onco-metabolite 2-Hydroxyglutarate or 2-HG, which occurs when two enzymes, IDH1 and IDH2, are genetically mutated. It is found in the tumor. 2-HG is thought to be responsible for the formation and maintenance of IDH-mutant gliomas.
The study is the first clinical trial to analyze a targeted therapy drug developed specifically to treat brain cancer.
Targeted therapies are designed to target specific molecules involved in the growth and spread of cancer cells. Unlike chemotherapy and other treatments that affect both cancer and healthy cells, targeted therapies only attack cancer cells with altered targets, minimizing damage to normal cells.
While there has been great progress in the use of targeted therapies to treat many types of cancer, developing targeted therapies specifically for brain tumors has remained a challenge due to the difficulty of penetrating the blood-brain barrier. Voracitinib is a brain-penetrant inhibitor, meaning it has the ability to cross the blood-brain barrier.
The study involved 331 people aged 12 and older who had been diagnosed with recurrent grade 2 glioma with IDH1 and IDH2 mutations and had undergone brain tumor surgery. From that group, 168 were randomly assigned to receive voracidine and 163 received placebo.
Among those who received vorasidenib, the disease did not progress for an average of 27.7 months, which was longer than 11.1 months for those who received placebo. And among those who received vorasidenib, 85.6% went for 18 months before the next treatment, and 83.4% went for 24 months between treatments.
The disease improved in only 28% of those receiving voracidinib, compared to 54% of those receiving placebo. And in September 2022, 30 months after the start of the study, 72% of patients in the voracitinib group were still taking the drug and their disease had not improved.
For patients in the placebo group whose cancer progressed during the study, doctors allowed them to switch to vorasidenib. The researchers noticed some side effects from vorasidenib. “This is the first targeted therapy to demonstrate unequivocal efficacy in this population and is a precursor to this disease,” Clousey said.
Benjamin Ellingson, director of the UCLA Brain Tumor Imaging Laboratory and a member of the Johnson Cancer Center, was a key participant in the research that led to the clinical trial. He participated in the radiographic evaluation of the tumors in the study, which confirmed the benefit of targeted therapy. The study’s first author is Dr. Ingo Mellinghoff of the Memorial Sloan Kettering Cancer Center. The co-author is Dr. Patrick Wen of the Dana-Farber Cancer Institute.
The study was funded by Servier Pharmaceuticals, which manufactures voracitinib. The drug is not yet approved by the FDA for clinical use.
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