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Clinical Trial
. 2016 Nov;18(11):1529-1537.
doi: 10.1093/neuonc/now133. Epub 2016 Jul 1.

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

Wolfgang Wick  1 , Patrick Roth  1 , Christian Hartmann  1 , Peter Hau  1 , Makoto Nakamura  1 , Florian Stockhammer  1 , Michael C Sabel  1 , Antje Wick  1 , Susanne Koeppen  1 , Ralf Ketter  1 , Peter Vajkoczy  1 , Ilker Eyupoglu  1 , Rolf Kalff  1 , Torsten Pietsch  1 , Caroline Happold  1 , Norbert Galldiks  1 , Friederike Schmidt-Graf  1 , Michael Bamberg  1 , Guido Reifenberger  1 , Michael Platten  1 , Andreas von Deimling  1 , Christoph Meisner  1 , Benedikt Wiestler  1 , Michael Weller  1 ; Neurooncology Working Group (NOA) of the German Cancer Society
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Clinical Trial

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

Wolfgang Wick et al. Neuro Oncol. 2016 Nov.

Erratum in

  • Corrigendum.
    [No authors listed] [No authors listed] Neuro Oncol. 2016 Nov;18(11):e1. doi: 10.1093/neuonc/now228. Neuro Oncol. 2016. PMID: 27738185 Free PMC article. No abstract available.

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.

Keywords: 1p/19q; CIMP; MGMT; anaplastic gliomas.

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Figures

Fig. 1.
Fig. 1.
CONSORT diagram of patient disposition. Forty-four patients (21 in arm A; 23 in arm B1/B2) were excluded from the intention-to-treat analysis because of study site closure, missing data, or withdrawal of consent. The numbers of patients with an event, a documented progression (PD) at the time of the analysis (31.12.2014), reaching the primary endpoint treatment failure (TF), and death (OS), and the number of patients in the biomarker subset are indicated.
Fig. 2.
Fig. 2.
Principal efficacy outcomes per treatment. Data of progression-free survival (PFS; (panel A), time-to-treatment failure (TTF; panel B), and overall survival (OS; panel C) were analyzed by treatment arm.
Fig. 3.
Fig. 3.
Efficacy outcomes according to histological and molecular subgroups. Data for time-to-treatment failure (TTF) according to histology (panel A) or molecular subtypes (panel B) and prediction error curves for TTF in Cox regression models including histology only, molecular classification only, or molecular classification and histology (both) (panel C) are depicted.
See this image and copyright information in PMC

Comment in

References

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