Wolfgang Wick, Patrick Roth, Christian Hartmann, Peter Hau, Makoto Nakamura, Florian Stockhammer, Michael C Sabel, Antje Wick, Susanne Koeppen, Ralf Ketter, Peter Vajkoczy, Ilker Eyupoglu, Rolf Kalff, Torsten Pietsch, Caroline Happold, Norbert Galldiks, Friederike Schmidt-Graf, Michael Bamberg, Guido Reifenberger, Michael Platten, Andreas von Deimling, Christoph Meisner, Benedikt Wiestler, Michael Weller
Journal: Neuro-oncology 2017;18(11):1529-1537
PMID: 27370396
BACKGROUND
Optimal treatment and precise classification for anaplastic glioma are needed.
METHODS
The objective for long-term follow-up of NOA-04 is to optimize the treatment sequence for patients with anaplastic gliomas. Patients were randomized 2:1:1 to receive the standard radiotherapy (RT) (arm A), procarbazine, lomustine and vincristine (PCV) (arm B1), or temozolomide (TMZ) (arm B2).
RESULTS
Primary endpoint was time-to-treatment-failure (TTF), defined as progression after 2 lines of therapy or any time before if no further therapy was administered. Exploratory analyses examined associations of molecular marker status with TTF, progression-free survival (PFS), and overall survival (OS). At 9.5 (95% CI: 8.6-10.2) years, no difference between arms (A vs B1/B2) was observed: median TTF (4.6 [3.4-5.1] y vs 4.4 [3.3-5.3) y), PFS (2.5 [1.3-3.5] y vs 2.7 [1.9-3.2] y), and OS (8 [5.5-10.3] y vs 6.5 [5.4-8.3] y). Oligodendroglial versus astrocytic histology-but more so the subgroups according to CpG island methylator phenotype (CIMP) and 1p/19q co-deletion status-revealed a strong prognostic value of CIMP with (CIMP) versus without 1p/19 co-deletion (CIMP) versus CIMP. but no differential efficacy of RT versus chemotherapy for any of the endpoints. PFS was better for PCV- than for TMZ-treated patients with CIMP tumors (HR B1 vs B2 0.39 [0.17-0.92], P = .031). In CIMP. tumors, hypermethylation of the O6-methyl-guanyl-DNA methyltransferase promoter (MGMT) provided a risk reduction for PFS with chemotherapy.
CONCLUSIONS
There is no differential activity of primary chemotherapy versus RT in any subgroup of anaplastic glioma. Molecular diagnosis is superior to histology.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00717210.
© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected].
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