MSGID: 1:317/3 647eb699   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    New drug delays progression of glioma, a deadly brain cancer    
    Study is first clinical trial analyzing a targeted therapy drug   
   specifically developed to treat brain tumors    
      
     Date:   
         June 5, 2023   
     Source:   
         University of California - Los Angeles Health Sciences   
     Summary:   
         Scientists have shown that a new targeted therapy drug can extend   
         the amount of time people with a subtype of glioma are on treatment   
         without their cancer worsening. The finding suggests a possible   
         new treatment option for people with the slow-growing but deadly   
         brain tumor.   
      
      
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   FULL STORY   
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   In an international study co-led by UCLA, scientists have shown that a   
   new targeted therapy drug can extend the amount of time people with a   
   subtype of glioma are on treatment without their cancer worsening. The   
   finding suggests a possible new treatment option for people with the   
   slow-growing but deadly brain tumor.   
      
   The team found the drug vorasidenib more than doubled progression-free   
   survival in people with recurrent grade 2 glioma with IDH1 and IDH2   
   mutations. Compared with people who received a placebo, those who took   
   vorasidenib went for nearly 17 more months without their cancer worsening,   
   delaying the time before they needed to begin chemotherapy and radiation.   
      
   The results were published in the New England Journal of Medicine and   
   presented today at the annual meeting of the American Society Clinical   
   Oncology in Chicago.   
      
   The type of glioma studied in the paper, recurrent grade 2 glioma with   
   IDH1 and IDH2 mutations, tends to affect younger people, often those in   
   their 30s. The current standard treatment, a combination of radiation   
   and chemotherapy, can cause neurological deficits that make it hard for   
   patients to learn, remember new things, concentrate or make everyday   
   decisions -- all of which can be especially challenging for people who   
   have young families or are in the early years of their professional lives.   
      
   Dr. Timothy Cloughesy, a professor of neuro-oncology at the David   
   Geffen School of Medicine at UCLA and co-senior author of the study,   
   said the availability of a treatment that enables patients to go for   
   longer periods of time between chemotherapy and radiation treatments   
   could have a major impact.   
      
   "We're always concerned about the delayed effects of radiation," said   
   Cloughesy, who is also a member of the UCLA Jonsson Comprehensive Cancer   
   Center. "Having the ability to hold off on getting radiation therapy   
   to the brain with an effective therapy is really critical and very   
   meaningful to this population of patients."  Vorasidenib is classified   
   as a dual inhibitor of mutant IDH1/2, meaning that it prevents the   
   formation and accumulation of the onco-metabolite 2- Hydroxyglutarate,   
   or 2-HG, that occurs when genetically altered versions of two enzymes,   
   IDH1 and IDH2, are present in a tumor. 2-HG is thought to be responsible   
   for the formation and maintenance of IDH-mutant gliomas.   
      
   The study is also the first clinical trial to analyze a targeted therapy   
   drug specifically developed to treat brain cancer.   
      
   Targeted therapies are designed to target specific molecules that are   
   involved in the growth and spread of cancer cells. Unlike chemotherapy   
   and other therapies that can affect both cancerous and healthy cells,   
   targeted therapies only attack cancer cells with the mutated target   
   while minimizing damage to normal cells.   
      
   While there has been great progress in using targeted therapies to treat   
   many types of cancer, development of targeted therapies for brain tumors   
   has been especially challenging because of the difficulty of getting   
   through the blood- brain barrier. Vorasidenib is a brain-penetrant   
   inhibitor, which means that it has the ability to cross the blood-brain   
   barrier.   
      
   The study involved 331 people aged 12 and older who had been diagnosed   
   with recurrent grade 2 glioma with the IDH1 and IDH2 mutations and who   
   had undergone brain tumor surgery. From that group, 168 were randomly   
   assigned to receive vorasidenib and 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 for   
   those who received the placebo. And among those who received vorasidenib,   
   85.6% went for 18 months before their next treatment, while 83.4% went   
   for 24 months between treatments.   
      
   The disease progressed in just 28% of people receiving vorasidenib,   
   compared to 54% of those receiving placebos. And as of September 2022,   
   which was 30 months after the study began, 72% of patients who were in   
   the vorasidenib group were still taking the drug and their disease had   
   not progressed.   
      
   For patients who were originally in the placebo group whose cancer   
   began to progress during the study, doctors permitted a switch to   
   vorasidenib. The researchers observed limited adverse side effects from   
   vorasidenib. "This is the first targeted treatment that shows unequivocal   
   efficacy in this population and is precedent-setting for this disease,"   
   Cloughesy said.   
      
   Benjamin Ellingson, director of the UCLA Brain Tumor Imaging Laboratory   
   and a member of the Jonsson Cancer Center, was a key participant in   
   the research that led to the clinical trial. He was involved in the   
   radiographic evaluation of tumors in the study, which confirmed that   
   there was a benefit of the targeted therapy. The study's first author   
   is Dr. Ingo Mellinghoff of Memorial Sloan- Kettering Cancer Center. The   
   co-senior author is Dr. Patrick Wen of the Dana- Farber Cancer Institute.   
      
   The study was sponsored by Servier Pharmaceuticals, which manufactures   
   vorasidenib. The drug has not yet been approved by the FDA for clinical   
   use.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Brain_Tumor # Personalized_Medicine # Lung_Cancer #   
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       * RELATED_TERMS   
             o Glioma o Malignant_melanoma o Occupational_therapy o   
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   ==========================================================================   
   Story Source: Materials provided by   
   University_of_California_-_Los_Angeles_Health_Sciences.   
      
   Original written by Denise Heady. Note: Content may be edited for style   
   and length.   
      
      
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   Journal Reference:   
      1. Ingo K. Mellinghoff, Martin J. van den Bent, Deborah T. Blumenthal,   
      Mehdi   
         Touat, Katherine B. Peters, Jennifer Clarke, Joe Mendez, Shlomit   
         Yust- Katz, Liam Welsh, Warren P. Mason, Franc,ois Ducray, Yoshie   
         Umemura, Burt Nabors, Matthias Holdhoff, Andreas F. Hottinger,   
         Yoshiki Arakawa, Juan M.   
      
         Sepulveda, Wolfgang Wick, Riccardo Soffietti, James R. Perry,   
         Pierre Giglio, Macarena de la Fuente, Elizabeth A. Maher, Steven   
         Schoenfeld, Dan Zhao, Shuchi S. Pandya, Lori Steelman, Islam   
         Hassan, Patrick Y. Wen, Timothy F. Cloughesy. Vorasidenib in IDH1-   
         or IDH2-Mutant Low-Grade Glioma. New England Journal of Medicine,   
         2023; DOI: 10.1056/NEJMoa2304194   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/06/230605181002.htm   
      
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