May 19, 2024

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First major breakthrough in the treatment of glioma in more than 20 years

First major breakthrough in the treatment of glioma in more than 20 years



 

NEJM: The first major breakthrough in the treatment of glioma in more than 20 years, greatly prolonging the survival of patients.

 

Grade 2 gliomas are incurable brain tumors, and IDH gene mutations are present in the vast majority of low-grade gliomas, which often appear in young people in their 30s and 40s. Current treatments include surgery, radiation therapy, and chemotherapy, which are effective treatments, but within a few years of treatment, patients develop signs of cognitive dysfunction typically seen in older adults.

 

The IDH1 and IDH2 genes encode isocitrate dehydrogenase 1 and 2, respectively, which catalyze the oxidative decarboxylation of isocitrate to form α-ketoglutarate (α-KG) . Mutations in IDH1/2 lead to the production of a large number of metabolites 2- HG, 2-HG can affect DNA methylation and histone modification, thereby inducing the occurrence and development of cancer .

 

Vorasidenib is a dual inhibitor of IDH1 and IDH2 mutant enzymes developed by Servier , which can be administered orally and can cross the blood-brain barrier to reach glioma sites, and has previously shown strong signs of efficacy in early clinical trials .

 

Recently, researchers from Memorial Sloan Kettering Cancer Center, Harvard Medical School Dana-Farber Cancer Institute, UCLA and other institutions published in the New England Journal of Medicine (NEJM) titled : Vorasidenib in IDH1- or IDH2 – Clinical trial paper for Mutant Low-Grade Glioma .

 

The phase 3 clinical trial data released this time showed that Vorasidenib significantly prolonged the progression-free survival of patients with grade 2 IDH-mutant glioma, and significantly prolonged the time for the next intervention (radiotherapy and chemotherapy) .

This is also the first major breakthrough in the treatment of low-grade glioma (grade 1 and 2) in more than 20 years , and the first targeted drug for this type of cancer to enter phase 3 clinical trials.

 

NEJM: The first major breakthrough in the treatment of glioma in more than 20 years, greatly prolonging the survival of patients

 

In this phase 3, global multicenter, double-blind, randomized controlled clinical trial, Servier’s IDH1/2 dual inhibitor Vorasidenib can help patients with grade 2 glioma with IDH1 or IDH2 mutations in the progression-free survival period The number of patients more than doubled (27.7 months vs 11.1 months) , and this therapy also greatly delayed the time of follow-up treatment with radiotherapy and chemotherapy.

 

Professor Patrick Y. Wen , director of the Neuro-Oncology Center at Dana-Farber Cancer Institute , one of the three leaders of the clinical trial , said that this is the first time in more than 20 years that a new drug has been introduced to treat these tumors, and Vorasidenib treatment can delay IDH mutations The need for radiation and chemotherapy in patients with glioma, by delaying these treatments, can delay cognitive impairment and preserve their quality of life.

 

This phase 3 clinical trial recruited 331 patients with grade 2 IDH-mutant glioma who underwent surgical resection of the tumor.

The enrolled patients did not need radiotherapy and chemotherapy immediately, but were in the observation and waiting period . During this time, they were randomly assigned to take Vorasidenib or a placebo.

 

The results showed that patients taking vorasidenib had a median progression-free survival of 27.7 months, compared with 11.1 months for patients taking a placebo.

Patients taking placebo had a median time to next treatment (radiotherapy and chemotherapy) of 17.8 months, while for patients taking Vorasidenib, the time to next treatment has not been determined as only 11.3% of patients taking Vorasidenib so far The patient’s disease has progressed to the point where the next treatment is required. In addition, the drug has a manageable safety profile.

 

NEJM: The first major breakthrough in the treatment of glioma in more than 20 years, greatly prolonging the survival of patients

 

 

Professor Patrick Y. Wen said that most low-grade glioma patients have IDH mutations, and this phase 3 clinical trial showed that IDH inhibitors can treat low-grade gliomas with IDH mutations.

In a field that has not seen a breakthrough in more than 20 years, this success will not only help many glioma patients, but also encourage more companies and researchers to devote resources to this field.

 

It is reported that Patrick Y. Wen is conducting a clinical trial of Vorasidenib combined with immunotherapy.

In addition, he also plans to conduct a clinical study of Vorasidenib combined with standard radiotherapy and chemotherapy.

 

 

 

 

 

 

 

Paper link :

https://www.nejm.org/doi/10.1056/NEJMoa2304194

NEJM: The first major breakthrough in the treatment of glioma in more than 20 years, greatly prolonging the survival of patients

(source:internet, reference only)


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