Gliomas are very aggressive brain tumors and any therapy capable of slowing down their progression is a gift of life for those affected and an opportunity to buy time until a definitive cure is found. The results of a new international clinical trial offer new hope because they have shown that an orally administered drug, vorasidenib, can halt the progression of diffuse low-grade (grade 2) gliomas with IDH protein gene mutations for several years. .
Vorasidenib targets a mutation in the IDH genes, which are found in 80% of low-grade gliomas. IDH-mutant gliomas account for approximately 20% of adult diffuse gliomas and are the most common malignant primary brain tumors. The study included 331 patients with a median age of 40 years. The drug prolonged progression-free survival by about 30 months compared with placebo and delayed the need for treatment by more than 40 months, in some cases indefinitely. Unprecedented results in this type of tumors.
The trial is called INDIGO and has been led by the United States with the collaboration of 77 centers and 10 countries, including Spain, where centers such as the Vall D’Ebron Hospital, in Barcelona, and the Ramón y Cajal, in Madrid, have participated. although the only Spanish researcher who signs the article published in The New England Journal of Medicine is Juan Manuel Sepúlveda, coordinator of the Neuro-oncology Unit of the University Hospital 12 de Octubre, in Madrid. The findings have also been presented at the ASCO Congress of the American Society for Medical Oncology, which is being held these days in Chicago.
Vorasidenib prolonged progression-free survival by about 30 months compared with placebo and delayed the need for treatment by more than 40 months
“This represents the first new treatment option for diffuse low-grade glioma in more than 20 years, and the first molecularly targeted therapy developed specifically for this disease,” said Ingo Mellinghoff, MD, chair of Memorial’s Department of Neurology. Sloan Kettering Cancer Center (MSK), which led the trial. “This potential therapy could be of great benefit to many people. Although we call them low-grade, these tumors are far from being a low-grade problem. They are incurable.”
Vorasidenib, effective in treating diffuse low-grade glioma
Diffuse low-grade gliomas in adults are usually slow-growing, but are still associated with a poor prognosis because they include symptoms such as thinking difficulties, blurred vision, numbness and weakness, and cause early death. In addition, they often affect young people who have to make the difficult decision between undergoing aggressive treatments after surgery, such as radiation therapy or chemotherapy, or waiting to see if their tumor grows, which causes them great anxiety.
Due to mutations in the genes called IDH1 and IDH2, tumor cells produce abnormally high amounts of enzymes that promote cancer growth. Vorasidenib, developed by Servier Pharmaceuticals and taken as a pill once daily, blocks the IDH1 and IDH2 mutant enzymes and could be an effective therapeutic alternative that does not impair a patient’s cognition or motor skills.
The 331 patients in the INDIGO trial were randomly divided into two groups to receive either vorasidenib or placebo once daily for four weeks. People in the vorasidenib group experienced a 61% reduced risk of tumor progression or death, and the treatment significantly delayed the need for more toxic therapy in the form of radium or chemo compared with placebo.
People in the vorasidenib group had a median progression-free survival (time until the tumor started to grow) that was more than twice that of the placebo group (27.7 months vs. 11.1 months). The median time until the next treatment was required was also much longer in the vorasidenib group. In addition, less than 10% of patients had serious side effects from the drug. The most frequent were elevations of liver enzymes, which were reversible.
Given the excellent results, it was decided that the study would be “unblinded” early so that people who were taking a placebo would have the opportunity to switch to vorasidenib. The drug is effective because it is designed to cross the blood-brain barrier, a network of blood vessels and tissue with cells in close proximity to each other.
“Having a therapy that penetrates the blood-brain barrier and kills specific cancer enzymes represents an important potential advance in the treatment of brain tumors,” says Dr. Mellinghoff. “We have been very fortunate at Memorial Sloan Kettering to play a leading role in this effort from the very beginning.” “Usually, we don’t see such amazing results in a trial, where one drug makes such a big difference in PFS,” concludes Dr. Mellinghoff.
Source: Memorial Sloan Kettering Cancer Center (MSK
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