Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide

• Verfasst von: Wick, Wolfgang [VerfasserIn]
• Verfasst von: Hartmann, Christian [VerfasserIn]
• Verfasst von: Wick, Antje [VerfasserIn]
• Verfasst von: Platten, Michael [VerfasserIn]
• Verfasst von: Deimling, Andreas von [VerfasserIn]
• Verfasst von: Wiestler, Benedikt [VerfasserIn]
• Titel: Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide
• Verf.angabe: 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, and Michael Weller for the Neurooncology Working Group (NOA) of the German Cancer Society
• E-Jahr: 2016
• Jahr: 1 July 2016
• Umfang: 9 S.
• Fussnoten: Gesehen am 27.11.2017
• Titel Quelle: Enthalten in: Neuro-Oncology
• Ort Quelle: Oxford : Oxford Univ. Press, 1999
• Jahr Quelle: 2016
• Band/Heft Quelle: 18(2016), 11, Seite 1529-1537
• ISSN Quelle: 1523-5866
• DOI: doi:10.1093/neuonc/now133
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1565742206

Abstract

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 CIMPpos with (CIMPcodel) versus without 1p/19 co-deletion (CIMPnon-codel) versus CIMPneg. but no differential efficacy of RT versus chemotherapy for any of the endpoints. PFS was better for PCV- than for TMZ-treated patients with CIMPcodel tumors (HR B1 vs B2 0.39 [0.17-0.92], P = .031). In CIMPneg. 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.