summary: A newly developed drug, Vorasidenib, has shown promising results in extending progression-free survival for patients with a subtype of glioma.
The international study found that patients taking vorasidenib could go nearly 17 more months without their cancer getting worse, delaying the need for radiation and chemotherapy. The drug specifically targets IDH1/2 mutations in recurrent grade II glioma, a slow-growing brain tumor that often affects younger individuals.
- Vorasidenib, a dual inhibitor of mutant IDH1/2, inhibits the accumulation of 2-HG, a tumor metabolite responsible for the formation and maintenance of IDH mutant gliomas.
- The trial included 331 patients, in which the vorasidenib-treated group showed significantly longer periods of disease progression (average of 27.7 months) than the placebo group (11.1 months).
- This study is the first clinical trial to examine a targeted therapy drug specifically designed for the treatment of brain cancer, in which Vorasidenib is able to cross the blood-brain barrier.
source: University of California
In an international study co-led by UCLA, scientists have shown that a new treatment drug can extend the period of time that people with a subtype of glioma undergo treatment without their cancer getting worse.
The findings point to a potential new treatment option for people with a slow-growing but deadly brain tumor.
The team found that vorasidenib doubled the rate of progression-free survival in people with recurrent grade II gliomas with IDH1 and IDH2 mutations. Compared with people who received a placebo, those who took vorasidenib went nearly 17 more months without their cancer getting worse, delaying the time before they needed to start chemotherapy and radiation.
The results are published in New England Journal of Medicine It was presented today at the annual meeting of the American Society of Clinical Oncology in Chicago.
The type of glioma studied in the paper, recurrent grade II glioma with IDH1 and IDH2 mutations, tends to affect young adults, often those in their 30s.
The current standard treatment, a combination of radiation and chemotherapy, can cause neurological deficits that make it difficult for patients to learn, remember new things, concentrate or make daily decisions — all of which can be particularly challenging for people with young families or in the early years. from their professional lives.
The availability of treatment that enables patients to go longer periods between chemotherapy and radiation therapy, said Dr. It can have a huge impact.
“We’re always concerned about the late effects of radiation,” said Clovisy, who is also a member of the UCLA Jonsson Comprehensive Cancer Center.
“Having the ability to delay radiation therapy reaching the brain with an effective treatment is really critical and very meaningful for this patient population.”
Vorasidenib has been classified as a dual inhibitor of mutant IDH1/2, which means that it prevents the formation and accumulation of the onco metabolite 2-Hydroxyglutarate, or 2-HG, which occurs when transgenic versions of two enzymes, IDH1 and IDH2, are present in a tumor. 2-HG is believed to be responsible for the formation and maintenance of IDH-transformed gliomas.
This study is also the first clinical trial to analyze a targeted therapy drug developed specifically for the treatment of 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 can affect both cancerous and healthy cells, targeted therapies only attack cancer cells with the mutated target while minimizing damage to normal cells.
While there have been significant advances in using targeted therapies to treat many types of cancer, developing targeted therapies for brain tumors has been particularly challenging due to the difficulty in traversing the blood-brain barrier. Vorasidenib is a brain penetration inhibitor, which means that it has the ability to cross the blood-brain barrier.
The study included 331 people aged 12 years or older who were diagnosed with recurrent grade 2 glioma with IDH1 and IDH2 mutations and who underwent surgery for a brain tumor. Of that group, 168 were randomized to receive vorasidenib and 163 received placebo.
Among those who received vorasidenib, disease did not progress for an average of 27.7 months, which was significantly longer than the 11.1 months for those who received placebo. Among those who received vorasidenib, 85.6% went 18 months before the next treatment, while 83.4% went 24 months between treatments.
Disease progression occurred in only 28% of people receiving vorasidenib, compared to 54% of those receiving placebo. And as of September 2022, 30 months after the study began, 72% of the patients who were in the vorasidenib group were still taking the drug and their disease had not progressed.
For patients who were originally in the placebo group and whose cancer had started to progress during the study, the doctors were allowed to switch to vorasidenib. Researchers have noted limited adverse side effects from vorasidenib.
“This is the first targeted therapy to show unequivocal efficacy in this population and is a first for this disease,” Clovisy said.
Benjamin Ellingson, MD, director of the UCLA Brain Tumor Imaging Laboratory and member of the Johnson Cancer Center, was a key participant in the research leading up to the clinical trial. He participated in the radiographic evaluation of tumors in the study, which confirmed that there is a benefit from targeted therapy.
The first author of the study is Dr. Ingo Mellinghoff of Memorial Sloan Kettering Cancer Center. Co-author is Dr. Patrick Wynne of the Dana-Farber Cancer Institute.
The study was sponsored by Servier Pharmaceuticals, which makes vorasidenib. The drug has not yet been approved by the Food and Drug Administration for clinical use.
About this brain cancer research news
author: Dennis Headey
source: University of California
communication; Dennis Headey – University of California
picture: Image credited to Neuroscience News
Original search: Closed access.
“Vorasidenib in low-grade IDH1- or IDH2-mutant gliomas” by Timothy Cloughesy et al. NEJM
Vorasidenib in low-grade IDH1- or IDH2-mutated gliomas
IDH – grade II gliomas are malignant brain tumors that cause significant disability and early death. Vorasidenib, an oral brain-penetrating inhibitor of mutant IDH1 and IDH2 enzymes, has shown primary activity in IDH-mutant gliomas.
In a double-blind phase 3 trial, we randomly assigned patients with residual or recurrent grade 2 metastatic glioma who had not undergone any prior treatment other than surgery to receive either oral vorasidenib (40 mg once daily) or a matching placebo at 28- Day sessions. The primary endpoint was imaging-based progression-free survival as assessed blindly by an independent review panel. The main secondary endpoint was the time to the next anticancer intervention. Crossover to vorasidenib from placebo was allowed when imaging-based disease progression was confirmed. Safety has also been evaluated.
A total of 331 patients were assigned to receive vorasidenib (168 patients) or placebo (163 patients). At a follow-up of 14.2 months, 226 patients (68.3%) continued to receive vorasidenib or placebo. Progression-free survival was significantly improved in the vorasidenib group compared to the placebo group (median progression-free survival, 27.7 months vs 11.1 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.27 to 0.56; P < 0.001).
The time to the next intervention was significantly improved in the vorasidenib group when compared to the placebo group (hazard ratio, 0.26; 95% CI, 0.15 to 0.43; P<0.001). Grade 3 or higher adverse events occurred in 22.8% of patients treated with vorasidenib and in 13.5% of those treated with placebo. An increase in alanine aminotransferase level of grade 3 or higher occurred in 9.6% of patients treated with vorasidenib and in none of the patients treated with placebo.
In patients with grade 2 IDH-mutated glioma, vorasidenib significantly improved progression-free survival and delayed time to the next intervention. (Funded by Servier; No. INDIGO ClinicalTrials.gov, NCT04164901. Opens in a new tab.)
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