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 MJ Neuro-Oncology Unit, Brain Tumour Centre at Erasmus MC Cancer Institute, Rotterdam, Netherlands. Electronic address: m.vandenbent@erasmusmc.nl.
- Baumert B Department of Radiation-Oncology (MAASTRO), Maastricht University Medical Centre (MUMC), Maastricht, Netherlands; GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre (MUMC), Maastricht, Netherlands; Department of Radiation-Oncology, University of Münster, Münster, Germany; Paracelsus Clinic, Osnabrück, Germany.
- Erridge SC Edinburgh Centre for Neuro-Oncology, Western General Hospital, University of Edinburgh, Edinburgh, UK.
- Vogelbaum MA Department of Neurosurgery, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA; Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH, USA.
- Nowak AK School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, Australia; Co-Operative Group for Neuro-Oncology, University of Sydney, Camperdown, NSW, Australia; Department of Medical Oncology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA, Australia.
- Sanson M Sorbonne Universités UPMC, University Paris VI, INSERM, CNRS, APHP, Institut du Cerveau et de la Moelle (ICM), Hôpital Pitié-Salpêtrière, F-75013, Paris, France.
- Brandes AA Medical Oncology Department, AUSL-IRCCS Scienze Neurologiche, Bologna, Italy.
- Clement PM Department of Oncology, KU Leuven, Leuven, Belgium; Department of General Medical Oncology, UZ Leuven, Leuven Cancer Institute, Leuven, Belgium.
- Baurain JF Medical Oncology Department, King Albert II Cancer Institute, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
- Mason WP Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
- Wheeler H Northern Sydney Cancer Centre, North Shore Hospital, St Leonards, NSW, Australia; Department of Medicine, University of Sydney, Sydney, NSW, Australia.
- Chinot OL Neuro-Oncology Division, Aix-Marseille University, AP-HM, Marseille, France.
- Gill S Department of Medical Oncology, Alfred Hospital, Melbourne, VIC, Australia.
- Griffin M Department of Clinical Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
- Brachman DG Department of Radiation Oncology, Barrow Neurological Institute, Phoenix, AZ, USA.
- Taal W Neuro-Oncology Unit, Brain Tumour Centre at Erasmus MC Cancer Institute, Rotterdam, Netherlands.
- Rudà R Department of Neuro-Oncology, City of Health and Science Hospital and University of Turin, Turin, Italy.
- Weller M Department of Neurology and Brain Tumour Centre, University Hospital and University of Zurich, Zurich, Switzerland.
- McBain C Department of Clinical Oncology, Christie NHS Foundation Trust, Manchester, UK.
- Reijneveld J VUmc Cancer Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Department of Neurology, VU University Medical Centre, Amsterdam, Netherlands; Department of Neurology, Academic Medical Centre, Amsterdam, Netherlands.
- Enting RH Department of Neurology, UMCG, University of Groningen, Groningen, Netherlands.
- Weber DC Department of Radiation Oncology, University Hospital of Geneva, Geneva, Switzerland.
- Lesimple T Department of Clinical Oncology, Comprehensive Cancer Center Eugène Marquis, Rennes, France.
- Clenton S Weston Park Hospital, Sheffield, UK.
- Gijtenbeek A Department of Neurology, Radboud University Medical Centre, Nijmegen, Netherlands.
- Pascoe S Department of Clinical Oncology, Plymouth Hospitals NHS Trust, Plymouth, UK.
- Herrlinger U Division of Clinical Neuro-Oncology, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany.
- Hau P Wilhelm Sander-Neuro-Oncology Unit and Department of Neurology, University Hospital Regensburg, Regensburg, Germany.
- Dhermain F Radiotherapy Department, Gustave Roussy University Hospital, Villejuif, France.
- van Heuvel I Neuro-Oncology Unit, Brain Tumour Centre at Erasmus MC Cancer Institute, Rotterdam, Netherlands.
- Stupp R Department of Medical Oncology, University Hospital and University of Zurich, Zurich, Switzerland.
- Aldape K Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
- Jenkins RB Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
- Dubbink HJ Department of Pathology, Brain Tumour Centre at Erasmus MC Cancer Institute, Rotterdam, Netherlands.
- Dinjens WNM Department of Pathology, Brain Tumour Centre at Erasmus MC Cancer Institute, Rotterdam, Netherlands.
- Wesseling P Department of Pathology, VU University Medical Centre, Amsterdam, Netherlands; Department of Pathology, Radboud University Medical Centre, Nijmegen, Netherlands.
- Nuyens S EORTC, Brussels, Belgium.
- Golfinopoulos V EORTC, Brussels, Belgium.
- Gorlia T EORTC, Brussels, Belgium.
- Wick W Neurologische Klinik und Nationales Zentrum für Tumorerkrankungen Universitätsklinik, Heidelberg, Germany.
- Kros JM Department of Pathology, Brain Tumour Centre at Erasmus MC Cancer Institute, Rotterdam, Netherlands.
- 2017-08-13
Published in:
- Lancet (London, England). - 2017
English
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.
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.
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.1016/S0140-6736(17)31442-3
- PMID 28801186
- Persistent URL
- https://folia.unifr.ch/global/documents/91070
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