The University of California scientists have discovered a new targeted therapy drug that can extend the treatment duration for individuals with a specific subtype of glioma, a deadly brain tumor. The drug, vorasidenib, was found to more than double the progression-free survival of patients with recurrent grade 2 glioma carrying IDH1 and IDH2 mutations. Compared to those who received a placebo, patients on vorasidenib experienced an additional 17 months without cancer progression, delaying the need for chemotherapy and radiation.
Recurrent grade 2 glioma with IDH1 and IDH2 mutations primarily affects younger individuals, often in their 30s. The current standard treatment, a combination of radiation and chemotherapy, can cause neurological deficits that hinder patients’ cognitive abilities, posing challenges for those with young families or early careers. Having a treatment that allows for longer intervals between chemotherapy and radiation sessions could have a significant impact, especially in terms of delaying the need for radiation therapy to the brain.
Vorasidenib, classified as a dual inhibitor of mutant IDH1/2, inhibits the production and accumulation of a harmful metabolite called 2-Hydroxyglutarate (2-HG). Mutated versions of the enzymes IDH1 and IDH2 contribute to the formation and maintenance of IDH-mutant gliomas, and 2-HG is believed to play a role in this process.
Targeted therapies aim to specifically target molecules involved in cancer cell growth and spread. Unlike chemotherapy and other treatments that affect both cancerous and healthy cells, targeted therapies solely attack cancer cells carrying the mutated target, minimizing harm to normal cells. Developing targeted therapies for brain tumors has been particularly challenging due to the blood-brain barrier, but vorasidenib is capable of crossing this barrier as a brain-penetrant inhibitor.
The scientists included 331 individuals aged 12 and older diagnosed with recurrent grade 2 glioma carrying IDH1 and IDH2 mutations, who had undergone brain tumor surgery. Among them, 168 were randomly assigned to receive vorasidenib, while 163 received placebos.
Patients receiving vorasidenib experienced an average delay of 27.7 months before disease progression, significantly longer than the 11.1 months for those on the placebo. Furthermore, 85.6% of vorasidenib recipients went 18 months without requiring the next treatment, and 83.4% went 24 months between treatments. Disease progression occurred in only 28% of individuals on vorasidenib, compared to 54% on placebos. As of September 2022, 72% of patients in the vorasidenib group were still taking the drug without disease progression.
In cases where patients originally in the placebo group experienced disease progression, doctors allowed them to switch to vorasidenib. The researchers noted minimal adverse effects associated with vorasidenib.