Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Oct 7;390(10103):1645-1653.
doi: 10.1016/S0140-6736(17)31442-3. Epub 2017 Aug 8.

Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study

Martin J van den Bent  1 , Brigitta Baumert  2 , Sara C Erridge  3 , Michael A Vogelbaum  4 , Anna K Nowak  5 , Marc Sanson  6 , Alba Ariela Brandes  7 , Paul M Clement  8 , Jean Francais Baurain  9 , Warren P Mason  10 , Helen Wheeler  11 , Olivier L Chinot  12 , Sanjeev Gill  13 , Matthew Griffin  14 , David G Brachman  15 , Walter Taal  16 , Roberta Rudà  17 , Michael Weller  18 , Catherine McBain  19 , Jaap Reijneveld  20 , Roelien H Enting  21 , Damien C Weber  22 , Thierry Lesimple  23 , Susan Clenton  24 , Anja Gijtenbeek  25 , Sarah Pascoe  26 , Ulrich Herrlinger  27 , Peter Hau  28 , Frederic Dhermain  29 , Irene van Heuvel  16 , Roger Stupp  30 , Ken Aldape  10 , Robert B Jenkins  31 , Hendrikus Jan Dubbink  32 , Winand N M Dinjens  32 , Pieter Wesseling  33 , Sarah Nuyens  34 , Vassilis Golfinopoulos  34 , Thierry Gorlia  34 , Wolfgang Wick  35 , Johan M Kros  32
Affiliations

Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study

Martin J van den Bent et al. Lancet. .

Erratum in

  • Department of Error.
    [No authors listed] [No authors listed] Lancet. 2017 Oct 7;390(10103):1644. doi: 10.1016/S0140-6736(17)32438-8. Epub 2017 Oct 5. Lancet. 2017. PMID: 29131794 No abstract available.

Abstract

Background: The role of temozolomide chemotherapy in newly diagnosed 1p/19q non-co-deleted anaplastic gliomas, which are associated with lower sensitivity to chemotherapy and worse prognosis than 1p/19q co-deleted tumours, is unclear. We assessed the use of radiotherapy with concurrent and adjuvant temozolomide in adults with non-co-deleted anaplastic gliomas.

Methods: This was a phase 3, randomised, open-label study with a 2 × 2 factorial design. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with WHO performance status scores of 0-2. The randomisation schedule was generated with the electronic EORTC web-based ORTA system. Patients were assigned in equal numbers (1:1:1:1), using the minimisation technique, to receive radiotherapy (59·4 Gy in 33 fractions of 1·8 Gy) alone or with adjuvant temozolomide (12 4-week cycles of 150-200 mg/m2 temozolomide given on days 1-5); or to receive radiotherapy with concurrent temozolomide 75 mg/m2 per day, with or without adjuvant temozolomide. The primary endpoint was overall survival adjusted for performance status score, age, 1p loss of heterozygosity, presence of oligodendroglial elements, and MGMT promoter methylation status, analysed by intention to treat. We did a planned interim analysis after 219 (41%) deaths had occurred to test the null hypothesis of no efficacy (threshold for rejection p<0·0084). This trial is registered with ClinicalTrials.gov, number NCT00626990.

Findings: At the time of the interim analysis, 745 (99%) of the planned 748 patients had been enrolled. The hazard ratio for overall survival with use of adjuvant temozolomide was 0·65 (99·145% CI 0·45-0·93). Overall survival at 5 years was 55·9% (95% CI 47·2-63·8) with and 44·1% (36·3-51·6) without adjuvant temozolomide. Grade 3-4 adverse events were seen in 8-12% of 549 patients assigned temozolomide, and were mainly haematological and reversible.

Interpretation: Adjuvant temozolomide chemotherapy was associated with a significant survival benefit in patients with newly diagnosed non-co-deleted anaplastic glioma. Further analysis of the role of concurrent temozolomide treatment and molecular factors is needed.

Funding: Schering Plough and MSD.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests

The other authors declare no competing interests.

Figures

Figure 1
Figure 1. Trial profile for patients included in the interim analysis
TT=intention-to-treat. *51 patients were still receiving temozolomide and 24 had missing data.
Figure 2
Figure 2. Survival in patients treated with or without adjuvant temozolomide
(A) Overall survival. (B) Progression-free survival. TMZ=temozolomide.
See this image and copyright information in PMC

Comment in

References

    1. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96. - PubMed
    1. Hegi ME, Diserens A-C, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352:997–1003. - PubMed
    1. van den Bent MJ, Carpentier AF, Brandes AA, et al. Adjuvant PCV improves progression free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized EORTC phase III trial. J Clin Oncol. 2006;24:2715–22. - PubMed
    1. Cairncross JG, Berkey B, Shaw E, et al. Phase III trial of chemotherapy plus radiotherapy (RT) versus RT alone for pure and mixed anaplastic oligodendroglioma (RTOG 9402): an intergroup trial by the RTOG, NCCTG, SWOG, NCI CTG and ECOG. J Clin Oncol. 2006;24:2707–14. - PubMed
    1. Cairncross JG, Ueki K, Zlatescu MC, et al. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst. 1998;90:1473–79. - PubMed

Associated data