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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.

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.

SUBMITTER: van den Bent MJ

PROVIDER: S-EPMC5806535 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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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.

van den Bent Martin J MJ Baumert Brigitta B Erridge Sara C SC Vogelbaum Michael A MA Nowak Anna K AK Sanson Marc M Brandes Alba Ariela AA Clement Paul M PM Baurain Jean Francais JF Mason Warren P WP Wheeler Helen H Chinot Olivier L OL Gill Sanjeev S Griffin Matthew M Brachman David G DG Taal Walter W Rudà Roberta R Weller Michael M McBain Catherine C Reijneveld Jaap J Enting Roelien H RH Weber Damien C DC Lesimple Thierry T Clenton Susan S Gijtenbeek Anja A Pascoe Sarah S Herrlinger Ulrich U Hau Peter P Dhermain Frederic F van Heuvel Irene I Stupp Roger R Aldape Ken K Jenkins Robert B RB Dubbink Hendrikus Jan HJ Dinjens Winand N M WNM Wesseling Pieter P Nuyens Sarah S Golfinopoulos Vassilis V Gorlia Thierry T Wick Wolfgang W Kros Johan M JM

Lancet (London, England) 20170808 10103

<h4>Background</h4>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.<h4>Methods</h4>This was a phase 3, randomised, open-label study with a 2 × 2 factorial design. Eligible patients were aged 18 year ...[more]

PMID: 28801186

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Project description:Abstract BACKGROUND EORTC study 26091 showed that addition of bevacizumab (BEV) to temozolomide (TMZ) does not improve overall survival (OS) or progression-free survival (PFS) in recurrent grade II and III 1p/19q intact gliomas; regardless of isocitrate dehydrogenase (IDH) mutational status. This abstract reports the neurocognitive functioning (NCF) outcomes. METHODS NCF was evaluated before randomization and at every 12 weeks during treatment using Hopkins Verbal Learning Test (Free Recall, Delayed Recall, and Delayed Recognition), Trail Making Test (TMT A/B); and Controlled Oral Word Association Test (COWA). RESULTS 148/155 patients had at least one NCF assessment. Compliance was 91.5% at baseline and dropped to 61.9% at week 60. Primary analysis (at 5% significance level) compared NCF at the last disease assessment before or at week 60 in patients who had at least one NCF assessment after baseline. Patients in the temozolomide+bevacizumab arm did not differ from patients in the temozolomide only arm. Except for Delayed Recognition, all NCF outcomes were positively associated with WHO performance status. TMT A (p=0.03), TMT B (p=0.006) and COWA (p<0.0001) were significantly worse in patients receiving steroids at study entry. Furthermore, delayed recognition was worse in patients with larger tumors (>26.5 vs <=26.5 mm; p=0.04). Memory performance was poorer in patients with tumors in the left hemisphere (Free Recall; p=0.0002), Delayed Recall; p<0.0001, Delayed Recognition; p=0.004). Except for Free Recall and Delayed Recognition, all other baseline raw scores were associated with OS in univariate analyses. In a multivariate Cox regression model, TMT B and tumor size were identified as independent OS prognostic factors while baseline WHO performance status and steroids use were not included. CONCLUSION At the group level patients in the temozolomide+bevacizumab arm do not differ from patients with temozolomide only, individual patients’ verbal memory capacity might negatively be affected by tumor volume and tumor location.

Dataset Information

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.

Publications

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.

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