학술논문
Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial
Document Type
article
Author
Weller, Michael; Butowski, Nicholas; Tran, David D; Recht, Lawrence D; Lim, Michael; Hirte, Hal; Ashby, Lynn; Mechtler, Laszlo; Goldlust, Samuel A; Iwamoto, Fabio; Drappatz, Jan; O'Rourke, Donald M; Wong, Mark; Hamilton, Mark G; Finocchiaro, Gaetano; Perry, James; Wick, Wolfgang; Green, Jennifer; He, Yi; Turner, Christopher D; Yellin, Michael J; Keler, Tibor; Davis, Thomas A; Stupp, Roger; Sampson, John H; investigators, ACT IV trial; Campian, Jian; Recht, Lawrence; Goldlust, Samuel; Becker, Kevin; Barnett, Gene; Nicholas, Garth; Desjardins, Annick; Benkers, Tara; Wagle, Naveed; Groves, Morris; Kesari, Santosh; Horvath, Zsolt; Merrell, Ryan; Curry, Richard; O'Rourke, James; Schuster, David; Mrugala, Maciej; Jensen, Randy; Trusheim, John; Lesser, Glenn; Belanger, Karl; Sloan, Andrew; Purow, Benjamin; Fink, Karen; Raizer, Jeffrey; Schulder, Michael; Nair, Suresh; Peak, Scott; Brandes, Alba; Mohile, Nimish; Landolfi, Joseph; Olson, Jon; Jennens, Ross; DeSouza, Paul; Robinson, Bridget; Crittenden, Marka; Shih, Kent; Flowers, Alexandra; Ong, Shirley; Connelly, Jennifer; Hadjipanayis, Costas; Giglio, Pierre; Mott, Frank; Mathieu, David; Lessard, Nathalie; Sepulveda, Sanchez Juan; Lövey, József; Wheeler, Helen; Inglis, Po-Ling; Hardie, Claire; Bota, Daniela; Lesniak, Maciej; Portnow, Jana; Frankel, Bruce; Junck, Larry; Thompson, Reid; Berk, Lawrence; McGhie, John; Macdonald, David; Saran, Frank; Soffietti, Riccardo; Blumenthal, Deborah; de, Sá Barreto Costa Marcos André
Source
The Lancet Oncology. 18(10)
Subject
Language
Abstract
BackgroundRindopepimut (also known as CDX-110), a vaccine targeting the EGFR deletion mutation EGFRvIII, consists of an EGFRvIII-specific peptide conjugated to keyhole limpet haemocyanin. In the ACT IV study, we aimed to assess whether or not the addition of rindopepimut to standard chemotherapy is able to improve survival in patients with EGFRvIII-positive glioblastoma.MethodsIn this randomised, double-blind, phase 3 trial, we recruited patients aged 18 years and older with glioblastoma from 165 hospitals in 22 countries. Eligible patients had newly diagnosed glioblastoma confirmed to express EGFRvIII by central analysis, and had undergone maximal surgical resection and completion of standard chemoradiation without progression. Patients were stratified by European Organisation for Research and Treatment of Cancer recursive partitioning analysis class, MGMT promoter methylation, and geographical region, and randomly assigned (1:1) with a prespecified randomisation sequence (block size of four) to receive rindopepimut (500 μg admixed with 150 μg GM-CSF) or control (100 μg keyhole limpet haemocyanin) via monthly intradermal injection until progression or intolerance, concurrent with standard oral temozolomide (150-200 mg/m2 for 5 of 28 days) for 6-12 cycles or longer. Patients, investigators, and the trial funder were masked to treatment allocation. The primary endpoint was overall survival in patients with minimal residual disease (MRD; enhancing tumour