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Scientists co-leading an international study, including researchers from UCLA, have demonstrated that a new targeted therapy drug called vorasidenib can prolong the duration of treatment without cancer progression in individuals with a specific subtype of glioma. This finding suggests a potential new treatment option for patients with this slow-growing but lethal brain tumor.
The study focused on recurrent grade 2 glioma with IDH1 and IDH2 mutations, which primarily affects younger individuals, often in their 30s. The standard treatment, a combination of radiation and chemotherapy, can result in neurological deficits that hinder patients’ ability to learn, remember, concentrate, and make decisions—particularly challenging for those with young families or in early stages of their careers.
Vorasidenib, a dual inhibitor of mutant IDH1/2, was found to more than double the progression-free survival in patients with this glioma subtype. Compared to those who received a placebo, individuals treated with vorasidenib experienced almost 17 additional months without cancer progression, delaying the need for chemotherapy and radiation.
The research results were published in the New England Journal of Medicine and presented at the annual meeting of the American Society of Clinical Oncology in Chicago.
Dr. Timothy Cloughesy, a professor of neuro-oncology at UCLA and co-senior author of the study, emphasized the significance of having a treatment that allows for longer intervals between chemotherapy and radiation sessions, thereby mitigating the delayed effects of radiation. He stated that this could have a major impact on patients in this particular population.Vorasidenib acts as a brain-penetrant inhibitor, effectively crossing the blood-brain barrier, which has been a significant challenge in developing targeted therapies for brain tumors.
The drug’s classification as a targeted therapy means it selectively attacks cancer cells with the mutated target, minimizing damage to healthy cells.The study involved 331 participants aged 12 and older diagnosed with recurrent grade 2 glioma with IDH1 and IDH2 mutations, who had undergone brain tumor surgery. Of these, 168 received vorasidenib and 163 received placebos.
Among those treated with vorasidenib, the disease did not progress for an average of 27.7 months, significantly longer than the 11.1 months for the placebo group. Moreover, 85.6% of patients in the vorasidenib group went for 18 months without requiring further treatment, while 83.4% went for 24 months.The disease progressed in only 28% of individuals receiving vorasidenib compared to 54% in the placebo group. As of September 2022, 72% of patients in the vorasidenib group were still on the drug without disease progression, which was 30 months after the study began.
For patients in the placebo group whose cancer progressed during the study, doctors allowed a switch to vorasidenib. The drug exhibited limited adverse side effects. Dr. Cloughesy described this targeted treatment as the first to demonstrate unequivocal efficacy in this patient population, setting a precedent for this disease.The study was sponsored by Servier Pharmaceuticals, the manufacturer of vorasidenib. However, the drug has not yet been approved by the FDA for clinical use.
Key participants in the research included Benjamin Ellingson, director of the UCLA Brain Tumor Imaging Laboratory,and Dr. Ingo Mellinghoff of Memorial Sloan-Kettering Cancer Center, the study’s first author. Dr. Patrick Wen of the Dana-Farber Cancer Institute also served as a co-senior author.
