Marizomib for patients with newly diagnosed glioblastoma: A randomized phase 3 trial. Journal Articles uri icon

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abstract

  • BACKGROUND: Standard treatment for patients with newly diagnosed glioblastoma includes surgery, radiotherapy (RT), and temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). The proteasome has long been considered a promising therapeutic target because of its role as a central biological hub in tumor cells. Marizomib is a novel pan-proteasome inhibitor that crosses the blood-brain barrier. METHODS: European Organisation for Research and Treatment of Cancer 1709/Canadian Cancer Trials Group CE.8 was a multicenter, randomized, controlled, open-label phase 3 superiority trial. Key eligibility criteria included newly diagnosed glioblastoma, age > 18 years and Karnofsky performance status > 70. Patients were randomized in a 1:1 ratio. The primary objective was to compare overall survival (OS) in patients receiving marizomib in addition to TMZ/RT→TMZ with patients receiving the only standard treatment in the whole population and in the subgroup of patients with MGMT promoter-unmethylated tumors. RESULTS: The trial was opened at 82 institutions in Europe, Canada, and the U.S. A total of 749 patients (99.9% of the planned 750) were randomized. OS was not different between the standard and the marizomib arm (median 17 vs. 16.5 months; HR = 1.04; P = .64). PFS was not statistically different either (median 6.0 vs. 6.3 months; HR = 0.97; P = .67). In patients with MGMT promoter-unmethylated tumors, OS was also not different between standard therapy and marizomib (median 14.5 vs. 15.1 months, HR = 1.13; P = .27). More CTCAE grade 3/4 treatment-emergent adverse events were observed in the marizomib arm than in the standard arm. CONCLUSIONS: Adding marizomib to standard temozolomide-based radiochemotherapy resulted in more toxicity, but did not improve OS or PFS in patients with newly diagnosed glioblastoma.

authors

  • Roth, Patrick
  • Gorlia, Thierry
  • Reijneveld, Jaap C
  • de Vos, Filip
  • Idbaih, Ahmed
  • Frenel, Jean-Sébastien
  • Le Rhun, Emilie
  • Sepulveda, Juan Manuel
  • Perry, James
  • Masucci, G Laura
  • Freres, Pierre
  • Hirte, Holger
  • Seidel, Clemens
  • Walenkamp, Annemiek
  • Lukacova, Slavka
  • Meijnders, Paul
  • Blais, Andre
  • Ducray, Francois
  • Verschaeve, Vincent
  • Nicholas, Garth
  • Balana, Carmen
  • Bota, Daniela A
  • Preusser, Matthias
  • Nuyens, Sarah
  • Dhermain, Fréderic
  • van den Bent, Martin
  • O'Callaghan, Chris J
  • Vanlancker, Maureen
  • Mason, Warren
  • Weller, Michael

publication date

  • September 5, 2024

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