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 - Ruda, 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 B.
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 - 2017/10/7
Y1 - 2017/10/7
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-codeleted anaplastic gliomas.Methods This was a phase 3, randomised, open-label study with a 2 x 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/m(2) temozolomide given on days 1-5); or to receive radiotherapy with concurrent temozolomide 75 mg/m(2) 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 pFindings 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-codeleted anaplastic gliomas.Methods This was a phase 3, randomised, open-label study with a 2 x 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/m(2) temozolomide given on days 1-5); or to receive radiotherapy with concurrent temozolomide 75 mg/m(2) 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 pFindings 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.
KW - BRAIN-TUMOR GROUP
KW - LOW-GRADE GLIOMA
KW - EUROPEAN ORGANIZATION
KW - OLIGODENDROGLIAL TUMORS
KW - IDH2 MUTATIONS
KW - III TRIAL
KW - PROCARBAZINE
KW - VINCRISTINE
KW - GLIOBLASTOMA
KW - CHEMOTHERAPY
U2 - 10.1016/S0140-6736(17)31442-3
DO - 10.1016/S0140-6736(17)31442-3
M3 - Article
SN - 0140-6736
VL - 390
SP - 1645
EP - 1653
JO - Lancet
JF - Lancet
IS - 10103
ER -