Trabectedin for recurrent WHO grade 2 or 3 meningioma: A randomized phase II study of the EORTC Brain Tumor Group (EORTC-1320-BTG)

Matthias Preusser, Antonio Silvani, Emilie le Rhun, Riccardo Soffietti, Giuseppe Lombardi, Juan Manuel Sepulveda, Petter Brandal, Lucy Brazil, Alice Bonneville-Levard, Veronique Lorgis, Elodie Vauleon, Jacoline Bromberg, Sara Erridge, Alison Cameron, Florence Lefranc, Paul M. Clement, Sarah Dumont, Marc Sanson, Charlotte Bronnimann, Carmen BalanáNiklas Thon, Joanne Lewis, Maximilian J. Mair, Philipp Sievers, Julia Furtner, Josef Pichler, Jordi Bruna, Francois Ducray, Jaap C. Reijneveld, Christian Mawrin, Martin Bendszus, Christine Marosi, Vassilis Golfinopoulos, Corneel Coens, Thierry Gorlia, Michael Weller, Felix Sahm, Wolfgang Wick

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12 Citations (Scopus)


BACKGROUND: No systemic treatment has been established for meningioma progressing after local therapies. METHODS: This randomized, multicenter, open-label, phase II study included adult patients with recurrent WHO grade 2 or 3 meningioma. Patients were 2:1 randomly assigned to intravenous trabectedin (1.5 mg/m2 every 3 weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). Secondary endpoints comprised overall survival (OS), objective radiological response, safety, quality of life (QoL) assessment using the QLQ-C30 and QLQ-BN20 questionnaires, and we performed tissue-based exploratory molecular analyses. RESULTS: Ninety patients were randomized (n = 29 in LOC, n = 61 in trabectedin arm). With 71 events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio [HR] = 1.42; 80% CI, 1.00-2.03; P = .294) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) and 21.1% (95% CI, 11.3%-32.9%), respectively. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR = 0.98; 95% CI, 0.54-1.76; P = .94). Grade ≥3 adverse events occurred in 44.4% of patients in the LOC and 59% of patients in the trabectedin arm. Enrolled patients had impeded global QoL and overall functionality and high fatigue before initiation of systemic therapy. DNA methylation class, performance status, presence of a relevant co-morbidity, steroid use, and right hemisphere involvement at baseline were independently associated with OS. CONCLUSIONS: Trabectedin did not improve PFS and OS and was associated with higher toxicity than LOC treatment in patients with non-benign meningioma. Tumor DNA methylation class is an independent prognostic factor for OS.
Original languageEnglish
Pages (from-to)755-767
Number of pages13
Issue number5
Publication statusPublished - 1 May 2022


  • DNA methylation class
  • clinical trial
  • meningioma
  • quality of life
  • trabectedin

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