Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated <i>MGMT</i> promoter

DOI PDF PDF 被引用文献2件
  • Michael Lim
    Department of Neurosurgery, Stanford University School of Medicine , Palo Alto, California , USA
  • Michael Weller
    Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich , Zurich , Switzerland
  • Ahmed Idbaih
    Sorbonne Université, Institut du Cerveau—Paris Brain Institute—ICM, Inserm, CNRS, AP-HP, Hôpital Universitaire La Pitié Salpêtrière , Paris , France
  • Joachim Steinbach
    Frankfurt Cancer Institute, Goethe University , Frankfurt , Germany
  • Gaetano Finocchiaro
    Unit of Molecular Neuro-Oncology, Neurological Institute C. Besta , Milan , Italy
  • Raju R Raval
    Translational Therapeutics Program, The Ohio State University Comprehensive Cancer Center , Columbus, Ohio , USA
  • George Ansstas
    Department of Medicine, Oncology Division, Washington University Medical School , St. Louis, Missouri , USA
  • Joachim Baehring
    Department of Neurology, Yale University School of Medicine , New Haven, Connecticut , USA
  • Jennie W Taylor
    Departments of Neurology and Neurological Surgery, University of California San Francisco , San Francisco, California , USA
  • Jerome Honnorat
    Neuro-Oncology Department, Hospices Civils de Lyon, SynatAc Team, Institute MeLis, INSERM U1314/CNRS UMR 5284, Université de Lyon, Université Claude Bernard Lyon 1 , Lyon , France
  • Kevin Petrecca
    Department of Neurology and Neurosurgery, Brain Tumour Research Centre, Montreal Neurological Institute-Hospital, McGill University , Montreal, Quebec , Canada
  • Filip De Vos
    Medical Oncology, University Medical Center Utrecht, Utrecht University , Utrecht , the Netherlands
  • Antje Wick
    Neurology Clinic, University of Heidelberg, National Center for Tumor Diseases , Heidelberg , Germany
  • Ashley Sumrall
    Neuro-Oncology Department, Levine Cancer Institute , Charlotte, North Carolina , USA
  • Solmaz Sahebjam
    Moffitt Cancer Center, University of South Florida , Tampa, Florida , USA
  • Ingo K Mellinghoff
    Department of Neurology and Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center , New York, New York , USA
  • Masashi Kinoshita
    Department of Neurosurgery, Kanazawa University , Ishikawa , Japan
  • Mustimbo Roberts
    Bristol Myers Squibb , Princeton, New Jersey , USA
  • Ruta Slepetis
    Bristol Myers Squibb , Princeton, New Jersey , USA
  • Deepti Warad
    Bristol Myers Squibb , Princeton, New Jersey , USA
  • David Leung
    Bristol Myers Squibb , Princeton, New Jersey , USA
  • Michelle Lee
    Syneos Health , Morrisville, North Carolina , USA
  • David A Reardon
    Center for Neuro-Oncology, Dana-Farber/Harvard Cancer Center , Boston, Massachusetts , USA
  • Antonio Omuro
    Department of Neurology, Yale University School of Medicine , New Haven, Connecticut , USA

抄録

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Nearly all patients with newly diagnosed glioblastoma experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ). The purpose of the phase III randomized CheckMate 548 study was to evaluate RT + TMZ combined with the immune checkpoint inhibitor nivolumab (NIVO) or placebo (PBO) in patients with newly diagnosed glioblastoma with methylated MGMT promoter (NCT02667587).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Patients (N = 716) were randomized 1:1 to NIVO [(240 mg every 2 weeks × 8, then 480 mg every 4 weeks) + RT (60 Gy over 6 weeks) + TMZ (75 mg/m2 once daily during RT, then 150-200 mg/m2 once daily on days 1-5 of every 28-day cycle × 6)] or PBO + RT + TMZ following the same regimen. The primary endpoints were progression-free survival (PFS) and overall survival (OS) in patients without baseline corticosteroids and in all randomized patients.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>As of December 22, 2020, median (m)PFS (blinded independent central review) was 10.6 months (95% CI, 8.9-11.8) with NIVO + RT + TMZ vs 10.3 months (95% CI, 9.7-12.5) with PBO + RT + TMZ (HR, 1.1; 95% CI, 0.9-1.3) and mOS was 28.9 months (95% CI, 24.4-31.6) vs 32.1 months (95% CI, 29.4-33.8), respectively (HR, 1.1; 95% CI, 0.9-1.3). In patients without baseline corticosteroids, mOS was 31.3 months (95% CI, 28.6-34.8) with NIVO + RT + TMZ vs 33.0 months (95% CI, 31.0-35.1) with PBO + RT + TMZ (HR, 1.1; 95% CI, 0.9-1.4). Grade 3/4 treatment-related adverse event rates were 52.4% vs 33.6%, respectively.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>NIVO added to RT + TMZ did not improve survival in patients with newly diagnosed glioblastoma with methylated or indeterminate MGMT promoter. No new safety signals were observed.</jats:p> </jats:sec>

収録刊行物

  • Neuro-Oncology

    Neuro-Oncology 24 (11), 1935-1949, 2022-05-02

    Oxford University Press (OUP)

被引用文献 (2)*注記

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