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首页> 外文期刊>Neuro-oncology >Depatuxizumab mafodotin in EGFR-amplified newly diagnosed glioblastoma: A phase Ⅲ randomized clinical trial
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Depatuxizumab mafodotin in EGFR-amplified newly diagnosed glioblastoma: A phase Ⅲ randomized clinical trial

机译:Depatuxizumab mafodotin in EGFR-amplified newly diagnosed glioblastoma: A phase Ⅲ randomized clinical trial

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摘要

Background. Approximately 50 of newly diagnosed glioblastomas (GBMs) harbor epidermal growth factor receptor gene amplification (EGFR-amp). Preclinical and early-phase clinical data suggested efficacy of depatuxizumab mafodotin (depatux-m), an antibody-drug conjugate comprised of a monoclonal antibody that binds activated EGFR (overexpressed wild-type and EGFRvlll-mutant) linked to a microtubule-inhibitor toxin in EGFR-amp GBMs. Methods. In this phase Ⅲ trial, adults with centrally confirmed, EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo. Corneal epitheliopathy was treated with a combination of protocol-specified prophylactic and supportive measures. There was 85 power to detect a hazard ratio (HR) ≤0.75 for overall survival (OS) at a 2.5 1-sided significance level (ie traditional two-sided p ≤ 0.05) by log-rank testing. Results. There were 639 randomized patients (median age 60, range 22-84; 62 men). Prespecified interim analysis found no improvement in OS for depatux-m over placebo (median 18.9 vs. 18.7 months, HR 1.02, 95 CI 0.82-1.26, 1-sided p = 0.63). Progression-free survival was longer for depatux-m than placebo (median 8.0 vs. 6.3 months; HR 0.84, 95 confidence interval CI 0.70-1.01, p = 0.029), particularly among those with EGFRvⅢ-mutant (median 8.3 vs. 5.9 months, HR 0.72, 95 CI 0.56-0.93, 1-sided p = 0.002) or MGMT unmethylated (HR 0.77,95 CI 0.61-0.97; 1-sided p= 0.012) tumors but without an OS improvement. Corneal epitheliopathy occurred in 94 of depatux-m-treated patients (61 grade 3-4), causing 12 to discontinue. Conclusions. Interim analysis demonstrated no OS benefit for depatux-m in treating EGFR-amp newly diagnosed GBM. No new important safety risks were identified.

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  • 来源
    《Neuro-oncology》 |2023年第2期|339-350|共12页
  • 作者单位

    Abbvie, Inc., North Chicago, Illinois, USA;

    Abbvie, Inc., North Chicago, Illinois, USA , Daiichi Sankyo, Inc., Basking Ridge, New Jersey, USA;

    Neuro-Oncology BranchDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Radiation-Oncology, University Hospital Leipzig, Leipzig, GermanyUniversity Medical Center Utrecht, Cancer Center, Utrecht, The NetherlandsDepartment of Neurosurgery, University of Texas Health Sciences Center, McGovern School of Medicine, Houston, Texas, USAFoundation for Clinical and Applied Cancer Research-FICMAC/Clinical andTranslational Oncology Group, BrainTumor Section, Bogota, Colombia, Luis Carlos Sarmiento Angulo CancerTreatment and Research Center - CITC, Bogota, ColombiaDepartment of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, ItalySverdlovsk Regional Oncology Center, Ekaterinburg, RussiaMetro Minnesota NCORP, Saint Paul, Minnesota, USACalvary Mater Newcastle, Waratah, New South Wales, AustraliaDepartment of Neurology, Cote dAzur University, Nice, FranceHeidelberg University Medical Center, Heidelberg, GermanyWinship Cancer Institute, Emory University, Atlanta, Georgia, USA , GenesisCare, Sydney, AustraliaMiami Cancer Institute, Baptist Hospital, Miami, Florida, USADivision of Neuro-Oncology , Departments of Neurology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian Hospital, NewYork, NewYork, USA, Herbert Irving Comprehensive Cancer Center, NewYork, NewYork, USARTOG Foundation Statistics and Data Management Center, American College of Radiology, Philadelphia, PennsylvaniaRadiation Oncology (in Neurological Surgery), Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian Hospital, NewYork, NewYork, USA, Herbert Irving Comprehensive Cancer Center, NewYork, NewYork, USALaboratory of PathologyNational Cancer Institute, Bethesda, Maryland, USA , CancerTherapies and Biology Group, Centre of Research Excellence in Brain Tumours, Olivia Newton-John Cancer Wellness and Research Centre, Austin Hospital, Heidelberg, Melbourne, Australia , LaTrobe UniDepartment of Medicine Ⅰ, Division of Oncology, Medical University of Vienna, Vienna, AustriaDepartment of Neuro-Oncology, Moffitt Cancer Center, Tampa, FloridaDepartment of Radiation Oncology, NewYork University, Grossman School of Medicine, NewYork, NewYork, USA, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, NewYork, NewYork, USARTOG Foundation Statistics and Data Management Center, American College of Radiology, Philadelphia, Pennsylvania, Incyte Corp., Wilmington, Delaware, USAOphthalmology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian Hospital, NewYork, NewYork, USANorthShore University HealthSystem, Department of Ophthalmology, University of Chicago Pritzker School of Medicine, Evanston, Illinois, USA;

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  • 正文语种 英语
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  • 关键词

    antibody drug conjugate; EGFR; depatuxizumab mafodotin; glioblastoma; phase Ⅲ;

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