Targeted therapy Vorasidenib offers hope for deadly brain tumors

Summary: A newly developed drug, Vorasidenib, has shown promise in prolonging progression-free survival for patients with a subtype of glioma.

The international study found that patients taking Vorasidenib could go almost 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 2 glioma, a slow-growing brain tumor that often affects younger individuals.


  1. Vorasidenib, a dual inhibitor of mutant IDH1/2, prevents the accumulation of 2-HG, an onco-metabolite responsible for the formation and maintenance of IDH-mutant gliomas.
  2. The study involved 331[ads1] patients, where the group treated with Vorasidenib showed significantly longer disease progression-free periods (on average 27.7 months) compared to the placebo group (11.1 months).
  3. This study is the first clinical trial investigating a targeted therapy drug specifically developed to treat brain cancer, with Vorasidenib able to cross the blood-brain barrier.

Source: UCLA

In an international study led by UCLA, researchers have shown that a new targeted therapy drug can extend the time people with a subtype of glioma are on treatment without their cancer getting worse.

The finding suggests a possible new treatment option for people with the slow-growing but deadly brain tumour.

The team found that the drug vorasidenib 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 took vorasidenib went almost 17 more months without their cancer getting worse, delaying the time before they needed to start chemotherapy and radiation.

The results were published in New England Journal of Medicine and presented today at the annual meeting of the American Society of Clinical Oncology in Chicago.

Targeted therapy Vorasidenib offers hope for deadly brain tumors
Vorasidenib is a brain-penetrating inhibitor, meaning it has the ability to cross the blood-brain barrier. Credit: Neuroscience News

The type of glioma studied in the paper, recurrent grade 2 glioma with IDH1 and IDH2 mutations, tends to affect younger people, 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 everyday decisions – all of which can be particularly challenging for people with young families or in the the first years of their professional life.

Dr. Timothy Cloughesy, professor of neuro-oncology at the David Geffen School of Medicine at UCLA and co-senior author of the study, said the availability of a treatment that allows patients to go for longer periods between chemotherapy and radiation treatments could have a big impact.

“We’re always concerned about the delayed effects of radiation,” said Cloughesy, who is also a member of the UCLA Jonsson Comprehensive Cancer Center.

“Having the ability to wait to get radiation to the brain with an effective therapy is very important and very meaningful for this patient group.”

Vorasidenib is classified as a dual inhibitor of mutant IDH1/2, meaning it prevents the formation and accumulation of the oncometabolite 2-Hydroxyglutarate, or 2-HG, which occurs when genetically altered versions of two enzymes, IDH1 and IDH2, are present in a tumor. 2-HG is thought to be responsible for the formation and maintenance of IDH mutant gliomas.

The study is also the first clinical study to analyze a targeted therapy drug specifically developed 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 therapies that can affect both cancer cells and healthy cells, targeted therapies attack only cancer cells with the mutated target while minimizing damage to normal cells.

While great progress has been made in using targeted therapies to treat many types of cancer, the development of targeted therapies for brain tumors has been particularly challenging due to the difficulty of crossing the blood-brain barrier. Vorasidenib is a brain-penetrating inhibitor, meaning it has the ability to cross the blood-brain barrier.

The study involved 331 people aged 12 years and older who had been diagnosed with recurrent grade 2 glioma with the IDH1 and IDH2 mutations and who had undergone brain tumor surgery. From that group, 168 were randomly assigned to vorasidenib and 163 received placebo.

Among those who received vorasidenib, the disease did not progress for an average of 27.7 months, significantly longer than the 11.1 months for those who received placebo. And among those who received vorasidenib, 85.6% went for 18 months before the next treatment, while 83.4% went for 24 months between treatments.

The disease developed in only 28% of people who received vorasidenib, compared with 54% of those who received placebo. And as of September 2022, which was 30 months after the study began, 72% of patients who were in the vorasidenib group were still taking the drug and their disease had not progressed.

For patients originally in the placebo group whose cancer began to progress during the study, doctors allowed them to switch to vorasidenib. The researchers observed limited side effects from vorasidenib.

“This is the first targeted therapy to show unequivocal efficacy in this population and is precedent-setting for this disease,” Cloughesy said.

Benjamin Ellingson, director of the UCLA Brain Tumor Imaging Laboratory and member of the Jonsson Cancer Center, was a key participant in the research that led to the clinical trial. He was involved in the radiographic evaluation of tumors in the study, which confirmed the benefit of targeted therapy.

The study’s first author is Dr. Ingo Mellinghoff from Memorial Sloan-Kettering Cancer Center. The co-senior author is Dr. Patrick Wen of the Dana-Farber Cancer Institute.

The study was sponsored by Servier Pharmaceuticals, which manufactures vorasidenib. The drug has not yet been approved by the FDA for clinical use.

About this brain cancer research news

Author: Denise Heady
Source: UCLA
Contact; Denise Heady – UCLA
Picture: Image is credited to Neuroscience News

Original research: Closed access.
“Vorasidenib in IDH1 or IDH2 Mutant Low-Grade Glioma” by Timothy Cloughesy et al. NO


Vorasidenib in IDH1 or IDH2 mutant low-grade glioma


Isocitrate dehydrogenase (IDH)-mutant grade 2 gliomas are malignant brain tumors that cause significant disability and premature death. Vorasidenib, an oral brain-penetrating inhibitor of mutant IDH1 and IDH2 enzymes, showed preliminary activity in IDH-mutant gliomas.


In a double-blind phase 3 study, we randomly assigned patients with residual or recurrent grade 2 IDH-mutant glioma who had not received any prior treatment other than surgery to receive either oral vorasidenib (40 mg once daily) or matched placebo for 28- daily cycles. The primary endpoint was imaging-based progression-free survival as assessed by a blinded independent review committee. The main secondary endpoint was the time to the next anticancer intervention. Crossover to vorasidenib from placebo was permitted upon confirmation of imaging-based disease progression. Safety was also assessed.


A total of 331 patients were assigned to vorasidenib (168 patients) or placebo (163 patients). At a median 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 with 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).

Time to next intervention was significantly improved in the vorasidenib group compared with 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 receiving vorasidenib and in 13.5% of those receiving placebo. An increased alanine aminotransferase level of grade 3 or higher occurred in 9.6% of patients receiving vorasidenib and in no patients receiving placebo.


In patients with grade 2 IDH-mutant glioma, vorasidenib significantly improved progression-free survival and delayed time to next intervention. (Funded by Servier; INDIGO number, NCT04164901. opens in new tab.)

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