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, Brigitta Baumert, Sara C. Erridge, Michael A. Vogelbaum, Anna K. Nowak, Marc Sanson, Alba Ariela Brandes, Paul M. Clement, Jean Francais Baurain, Warren P. Mason, Helen Wheeler, Olivier L. Chinot, Sanjeev Gill, Matthew Griffin, David G. Brachman, Walter Taal, Roberta Rudà, Michael Weller, Catherine McBain, Jaap ReijneveldRoelien H. Enting, Damien C. Weber, Thierry Lesimple, Susan Clenton, Anja Gijtenbeek, Sarah Pascoe, Ulrich Herrlinger, Peter Hau, Frederic Dhermain, Irene van Heuvel, Roger Stupp, Ken Aldape, Robert Brian Jenkins, Hendrikus Jan Dubbink, Winand N.M. Dinjens, Pieter Wesseling, Sarah Nuyens, Vassilis Golfinopoulos, Thierry Gorlia, Wolfgang Wick, Johan M. Kros

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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.

Original languageEnglish (US)
JournalThe Lancet
DOIs
StateAccepted/In press - Jan 1 2017

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temozolomide
Glioma
Therapeutics
Radiotherapy
Survival
Drug Therapy

ASJC Scopus subject areas

  • Medicine(all)

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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.; Baumert, Brigitta; Erridge, Sara C.; Vogelbaum, Michael A.; Nowak, Anna K.; Sanson, Marc; Brandes, Alba Ariela; Clement, Paul M.; Baurain, Jean Francais; Mason, Warren P.; Wheeler, Helen; Chinot, Olivier L.; Gill, Sanjeev; Griffin, Matthew; Brachman, David G.; Taal, Walter; Rudà, Roberta; Weller, Michael; McBain, Catherine; Reijneveld, Jaap; Enting, Roelien H.; Weber, Damien C.; Lesimple, Thierry; Clenton, Susan; Gijtenbeek, Anja; Pascoe, Sarah; Herrlinger, Ulrich; Hau, Peter; Dhermain, Frederic; van Heuvel, Irene; Stupp, Roger; Aldape, Ken; Jenkins, Robert Brian; Dubbink, Hendrikus Jan; Dinjens, Winand N.M.; Wesseling, Pieter; Nuyens, Sarah; Golfinopoulos, Vassilis; Gorlia, Thierry; Wick, Wolfgang; Kros, Johan M.

In: The Lancet, 01.01.2017.

Research output: Contribution to journalArticle

van den Bent, MJ, Baumert, B, Erridge, SC, Vogelbaum, MA, Nowak, AK, Sanson, M, Brandes, AA, Clement, PM, Baurain, JF, Mason, WP, Wheeler, H, Chinot, OL, Gill, S, Griffin, M, Brachman, DG, Taal, W, Rudà, R, Weller, M, McBain, C, Reijneveld, J, Enting, RH, Weber, DC, Lesimple, T, Clenton, S, Gijtenbeek, A, Pascoe, S, Herrlinger, U, Hau, P, Dhermain, F, van Heuvel, I, Stupp, R, Aldape, K, Jenkins, RB, Dubbink, HJ, Dinjens, WNM, Wesseling, P, Nuyens, S, Golfinopoulos, V, Gorlia, T, Wick, W & Kros, JM 2017, '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', The Lancet. https://doi.org/10.1016/S0140-6736(17)31442-3
van den Bent, Martin J. ; Baumert, Brigitta ; Erridge, Sara C. ; Vogelbaum, Michael A. ; Nowak, Anna K. ; Sanson, Marc ; Brandes, Alba Ariela ; Clement, Paul M. ; Baurain, Jean Francais ; Mason, Warren P. ; Wheeler, Helen ; Chinot, Olivier L. ; Gill, Sanjeev ; Griffin, Matthew ; Brachman, David G. ; Taal, Walter ; Rudà, Roberta ; Weller, Michael ; McBain, Catherine ; Reijneveld, Jaap ; Enting, Roelien H. ; Weber, Damien C. ; Lesimple, Thierry ; Clenton, Susan ; Gijtenbeek, Anja ; Pascoe, Sarah ; Herrlinger, Ulrich ; Hau, Peter ; Dhermain, Frederic ; van Heuvel, Irene ; Stupp, Roger ; Aldape, Ken ; Jenkins, Robert Brian ; Dubbink, Hendrikus Jan ; Dinjens, Winand N.M. ; Wesseling, Pieter ; Nuyens, Sarah ; Golfinopoulos, Vassilis ; Gorlia, Thierry ; Wick, Wolfgang ; Kros, Johan M. / 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. In: The Lancet. 2017.
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title = "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.",
author = "{van den Bent}, {Martin J.} and Brigitta Baumert and Erridge, {Sara C.} and Vogelbaum, {Michael A.} and Nowak, {Anna K.} and Marc Sanson and Brandes, {Alba Ariela} and Clement, {Paul M.} and Baurain, {Jean Francais} and Mason, {Warren P.} and Helen Wheeler and Chinot, {Olivier L.} and Sanjeev Gill and Matthew Griffin and Brachman, {David G.} and Walter Taal and Roberta Rud{\`a} and Michael Weller and Catherine McBain and Jaap Reijneveld and Enting, {Roelien H.} and Weber, {Damien C.} and Thierry Lesimple and Susan Clenton and Anja Gijtenbeek and Sarah Pascoe and Ulrich Herrlinger and Peter Hau and Frederic Dhermain and {van Heuvel}, Irene and Roger Stupp and Ken Aldape and Jenkins, {Robert Brian} and Dubbink, {Hendrikus Jan} and Dinjens, {Winand N.M.} and Pieter Wesseling and Sarah Nuyens and Vassilis Golfinopoulos and Thierry Gorlia and Wolfgang Wick and Kros, {Johan M.}",
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month = "1",
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journal = "The Lancet",
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TY - JOUR

T1 - 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

T2 - A phase 3, randomised, open-label intergroup study

AU - van den Bent, Martin J.

AU - Baumert, Brigitta

AU - Erridge, Sara C.

AU - Vogelbaum, Michael A.

AU - Nowak, Anna K.

AU - Sanson, Marc

AU - Brandes, Alba Ariela

AU - Clement, Paul M.

AU - Baurain, Jean Francais

AU - Mason, Warren P.

AU - Wheeler, Helen

AU - Chinot, Olivier L.

AU - Gill, Sanjeev

AU - Griffin, Matthew

AU - Brachman, David G.

AU - Taal, Walter

AU - Rudà, Roberta

AU - Weller, Michael

AU - McBain, Catherine

AU - Reijneveld, Jaap

AU - Enting, Roelien H.

AU - Weber, Damien C.

AU - Lesimple, Thierry

AU - Clenton, Susan

AU - Gijtenbeek, Anja

AU - Pascoe, Sarah

AU - Herrlinger, Ulrich

AU - Hau, Peter

AU - Dhermain, Frederic

AU - van Heuvel, Irene

AU - Stupp, Roger

AU - Aldape, Ken

AU - Jenkins, Robert Brian

AU - Dubbink, Hendrikus Jan

AU - Dinjens, Winand N.M.

AU - Wesseling, Pieter

AU - Nuyens, Sarah

AU - Golfinopoulos, Vassilis

AU - Gorlia, Thierry

AU - Wick, Wolfgang

AU - Kros, Johan M.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

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