Major Advancement in Glioma Treatment: Promising New Drug Delays Progression of Lethal Brain Cancer
According to a global study co-led by UCLA, a groundbreaking targeted therapy drug named vorasidenib has demonstrated the ability to more than double the period during which patients with a specific subtype of glioma remain free from disease progression. By inhibiting the mutant IDH1/2 enzymes, this drug effectively delays the need for chemotherapy and radiation by nearly 17 months, offering a revolutionary treatment option for this highly lethal brain tumor.
This study represents the first clinical trial dedicated to evaluating a targeted therapy designed specifically to address brain tumors.
The drug vorasidenib, a targeted therapy, has displayed encouraging outcomes in delaying the advancement of a particular form of glioma—a slow-growing yet deadly brain cancer. After studying 331 individuals afflicted with this disease, researchers found that the drug effectively extended the period of time before the cancer deteriorated, and no adverse effects were observed. The urgent need for new glioma treatments arises from the fact that existing therapies, such as chemotherapy and radiation, often lead to neurological impairments.
In an international collaboration led by the University of California, Los Angeles (UCLA), scientists have achieved a significant breakthrough by showcasing the ability of a newly developed targeted therapy drug to lengthen the treatment duration without disease progression in individuals diagnosed with a subtype of glioma. This discovery suggests a potential novel treatment option for patients grappling with this slow-growing yet fatal brain tumor.
The researchers discovered that vorasidenib, a drug that inhibits mutant IDH1/2 enzymes, more than doubled the progression-free survival rate in patients with recurrent grade 2 glioma harboring IDH1 and IDH2 mutations. Compared to those who received a placebo, individuals treated with vorasidenib experienced an additional 17 months without their cancer worsening, thus postponing the need for chemotherapy and radiation therapy.
The findings of this study were published in the New England Journal of Medicine and presented on June 4, 2023, during the annual meeting of the American Society Clinical Oncology in Chicago.
The glioma subtype investigated in this research, characterized by recurrent grade 2 glioma with IDH1 and IDH2 mutations, predominantly affects younger individuals, often in their 30s. The standard treatment currently available, a combination of radiation and chemotherapy, often causes neurological impairments that hinder patients’ ability to learn, remember, concentrate, or make everyday decisions. These challenges are particularly daunting for individuals with young families or those in the early stages of their careers.
Dr. Timothy Cloughesy, a neuro-oncology professor at the David Geffen School of Medicine at UCLA and co-senior author of the study, emphasized the potential impact of a treatment that enables longer intervals between chemotherapy and radiation sessions.
“We’re always concerned about the delayed effects of radiation,” stated Cloughesy, who is also affiliated with the UCLA Jonsson Comprehensive Cancer Center. “Having the ability to delay radiation therapy to the brain with an effective therapy is truly critical and immensely meaningful for this patient population.”
Vorasidenib is classified as a dual inhibitor of mutant IDH1/2 enzymes, effectively preventing the formation and accumulation of the onco-metabolite 2-Hydroxyglutarate (2-HG) that occurs in tumors featuring genetically altered versions of the IDH1 and IDH2 enzymes. 2-HG is believed to be responsible for the development and maintenance of IDH-mutant gliomas.
This study marks the first clinical trial to evaluate a targeted therapy drug specifically designed to treat brain cancer.
Targeted therapies are designed to selectively attack molecules involved in the growth and spread of cancer cells. Unlike chemotherapy and other therapies that impact both cancerous and healthy cells, targeted therapies exclusively target cancer cells with the specific mutated target while minimizing harm to normal cells.
Although significant progress has been made in the use of targeted therapies for various types of cancer, developing such therapies for brain tumors has proven particularly challenging due to the blood-brain barrier’s formidable nature. Vorasidenib, as a brain-penetrant inhibitor, possesses the ability to cross this barrier.
The study involved 331 participants aged 12 and older who had been diagnosed with recurrent grade 2 glioma featuring IDH1 and IDH2 mutations and had undergone brain tumor surgery. Among this group, 168 individuals were randomly assigned to receive vorasidenib, while 163 received placebos.
Among those who received vorasidenib, the disease did not progress for an average of 27.7 months, significantly longer than the 11.1 months observed in those who received the placebo. Moreover, 85.6% of the vorasidenib-treated group were able to delay their subsequent treatment for 18 months, while 83.4% were able to postpone it for 24 months.
Disease progression occurred in only 28% of individuals receiving vorasidenib, compared to 54% of those receiving placebos. As of September 2022, which marked 30 months since the study commenced, 72% of patients in the vorasidenib group were still taking the drug, and their disease had not progressed.
In cases where patients initially received placebos and experienced cancer progression during the study, doctors permitted a switch to vorasidenib. The researchers noted limited adverse side effects from vorasidenib. Dr. Cloughesy affirmed, “This is the first targeted treatment that shows unequivocal efficacy in this population and is precedent-setting for this disease.”
Reference: “Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma” by Ingo K. Mellinghoff, M.D., Martin J. van den Bent, M.D., Deborah T. Blumenthal, M.D., Mehdi Touat, M.D., Katherine B. Peters, M.D., Jennifer Clarke, M.D., M.P.H., Joe Mendez, M.D., Shlomit Yust-Katz, M.D., Liam Welsh, M.D., Ph.D., Warren P. Mason, M.D., François Ducray, M.D., Yoshie Umemura, M.D., Burt Nabors, M.D., Matthias Holdhoff, M.D., Andreas F. Hottinger, M.D., Ph.D., Yoshiki Arakawa, M.D., Juan M. Sepulveda, M.D., Wolfgang Wick, M.D., Riccardo Soffietti, M.D., James R. Perry, M.D., Pierre Giglio, M.D., Macarena de la Fuente, M.D., Elizabeth A. Maher, M.D., Steven Schoenfeld, M.S., Dan Zhao, Ph.D., Shuchi S. Pandya, M.D., Lori Steelman, M.S., Islam Hassan, M.D., Patrick Y. Wen, M.D., and Timothy F. Cloughesy, M.D., 4 June 2023, New England Journal of Medicine.
DOI: 10.1056/NEJMoa2304194
Benjamin Ellingson, director of the UCLA Brain Tumor Imaging Laboratory and a member of the Jonsson Cancer Center, played a crucial role in the research leading to the clinical trial. He contributed to the radiographic evaluation of tumors in the study, confirming the benefits of the targeted therapy. The study’s primary author is Dr. Ingo Mellinghoff from Memorial Sloan-Kettering Cancer Center, and the co-senior author
