2019 ASCO Annual Meeting!
Session: Central Nervous System Tumors
Type: Oral Abstract Session
Time: Monday June 3, 1:15 PM to 4:15 PM
Second interim and first molecular analysis of the EORTC randomized phase III intergroup CATNON trial on concurrent and adjuvant temozolomide in anaplastic glioma without 1p/19q codeletion.
Central Nervous System Tumors
Central Nervous System Tumors
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 2000)
Author(s): Martin J. Van Den Bent, Sara Erridge, Michael A. Vogelbaum, Anna K. Nowak, Marc Sanson, Alba Ariela Brandes, Wolfgang Wick, Paul M. Clement, Jean-Francois Baurain, Warren P. Mason, Helen Wheeler, Michael Weller, Kenneth D. Aldape, Pieter Wesseling, Johan M. Kros, Mircea Tesileanu, Vassilis Golfinopoulos, Thierry Gorlia, Brigitta G. Baumert, Pim French; Erasmus MC Cancer Centre, Rotterdam, Netherlands; Edinburgh Cancer Research UK Centre, Edinburgh, United Kingdom; Cleveland Clinic, Cleveland, OH; Sir Charles Gairdner Hospital, Perth, WA, Australia; Universite Pierre Et Marie Curie-Paris 6, Centre de Recherche de L'institut Du Cerveau et de la Moelle Épinière (CRICM), Neurologie 2, Paris, France; AUSL-IRCCS Institute of Neurological Sciences, Bologna, Italy; National Center for Tumor Diseases (NCT), UKHD and German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Oncology, KU Leuven, Leuven Cancer Institute, Leuven, Belgium; Department of Medical Oncology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Bruxelles, Belgium; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Royal North Shore Hospital, Department of Oncology, St Leonards, Australia; Laboratory of Molecular Neuro-Oncology, Department of Neurology, and Neuroscience Center Zurich, University Hospital and University of Zurich, Zurich, Switzerland; The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Pathology, VU University Medical Center, Amsterdam, Netherlands; Department of Neuropathology, Erasmus Medical Center – Cancer Institute, Rotterdam, Netherlands; Erasmus MC Cancer Institute, Rotterdam, Netherlands; EORTC Headquarters, Brussels, Belgium; Dept Radiation-Oncology, University Hospital Bonn, Germnany, Bonn, Germany; Erasmus MC, Rotterdam, Netherlands
Background: The 1st interim analysis of the CATNON trial showed benefit from adjuvant (adj) temozolomide (TMZ) on overall survival (OS) but remained inconclusive about concurrent (conc) TMZ. A 2nd interim analysis was planned after 356 events. Methods: The 2x2 factorial design phase III CATNON trial randomized 751 adult patients with newly diagnosed non-codeleted anaplastic glioma to either 59.4 Gy radiotherapy (RT) alone; the same RT with concTMZ; the same RT and 12 cycles of adjTMZ or the same RT with both concTMZ and adjTMZ (doi: 10.1016/S0140-6736(17)31442-3). MGMT promoter methylation (MGMTmeth) status was re-assessed with the Infinium Methylation EPIC Beadchip using the MGMT_STP27 model. Isocitrate dehydrogenase 1 and 2 (IDH) mutation (mt) status was assessed with glioma targeted Agilent SureSelect baits sequence using an Illumina HiSeq2500 Rapid PE100. Results: With a median follow-up of 56 months and 356 events, the hazard ratio (HR) for OS adjusted for stratification factors after concTMZ was 0.968 (99.1% CI 0.73, 1.28). 5-year OS was 50.2% with and 52.7% without concTMZ (95% CI [44.4, 55.7] and [46.9, 58.1]). An IDHmt was found in 335 of 480 assessed cases (70%). Median OS was 19 mo (95% CI 16.3, 22.3) in IDHwt tumors and 116 mo (95% CI 82.0, 116.6) in IDHmt tumors. HR for OS after concTMZ in patients with known IDH status. Clinical trial information: NCT00626990IDHmt was predictive of benefit from adjTMZ (IDHmt HR: 0.41, 95% CI 0.27, 0.64; IDHwt: HR 1.05, 95% CI 0.73, 1.52; interaction test p = 0.001). In IDHmt patients that received adjTMZ, the HR for OS after concTMZ was 0.71 (95% CI 0.35, 1.42, p=0.32). MGMTmeth was found in 288 of 410 assessed cases (70%), interaction test for concTMZ (p = 0.092) and adjTMZ (p = 0.166) did not reach statistical significance. Conclusions: In the entire study cohort, concTMZ did not increase OS. However, in IDHmt tumors a trend towards benefit of concTMZ is present. AdjTMZ increased OS in IDHmt but not in IDHwt tumors. The ongoing molecular analyses and further follow-up will allow full assessment of efficacy in the molecular subgroups.
|Patients||n||events||HR [95% CI]||interaction test|
|wt||145||120||1.27 [0.89, 1.82] p = 0.19||p = 0.016|
|mt||335||92||0.67 [0.44, 1.03], p = 0.06|