162108-176

Results of the interim analysis of the EORTC randomized phase III CATNON trial on concurrent and adjuvant temozolomide in anaplastic glioma without 1p/19q co-deletion: An Intergroup trial.

Category: 
Central Nervous System Tumors
Session Type and Session Title: 
Oral Abstract Session, Central Nervous System Tumors
Abstract Number: 

LBA2000

Citation: 
J Clin Oncol 34, 2016 (suppl; abstr LBA2000)
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, Olivier L. Chinot, Michael Weller, Vassilis Golfinopoulos, Ken Aldape, Winand N.M. Dinjens, Pieter Wesseling, Thierry Gorlia, Johan M Kros, Brigitta G. Baumert; Erasmus MC Cancer Center, Rotterdam, Netherlands; South East Scotland Cancer Centre, Edinburgh, United Kingdom; Cleveland Clinic Brain Tumor I, 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; Azienda USL Bellaria-Maggiore Hospital, Bologna, Italy; Neurology Clinic, Heidelberg, Germany; UZ Leuven-Gasthuisberg, Leuven, Belgium; Oncologie Médicale Cliniques Universitaires Saint-Luc, Brussels, Belgium; Princess Margaret Hospital, Toronto, ON, Canada; Royal North Shore Hospital, Department of Oncology, St Leonards, Australia; Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France; University Hospital Zurich, Zurich, Switzerland; EORTC, Brussels, Belgium; Toronto General Hospital/Research Institute (UHN), Toronto, ON, Canada; Erasmus University Medical Center, Rotterdam, Netherlands; Department of Pathology, VU University Medical Center, Amsterdam, Netherlands; EORTC Data Centre, Brussels, Belgium; Department of Neuropathology, Erasmus MC – Cancer Center, Rotterdam, Netherlands; University of Bonn Medical Centre, Bonn, Germany

Abstract Disclosures

Abstract: 

Background: The benefit of adding chemotherapy to radiotherapy (RT) in newly diagnosed anaplastic glioma without 1p/19q co-deletion is unknown. The CATNON trial investigated the impact of adjuvant and/or concurrent chemotherapy with temozolomide (TMZ) in these tumors. Methods: Eligible were patients with newly diagnosed WHO grade III glioma without 1p/19q co-deletion, ≥ 18 years, and WHO performance status (PS) 0-2. All patients received RT 59.4 Gy in 33 fractions, and in a 2 x 2 factorial design were randomized to: RT alone; RT with concurrent daily 75 mg/m2 TMZ; RT followed with 12 cycles of 150-200 mg/m2 adjuvant TMZ day 1-5/4 weeks; or RT with both concurrent and 12 cycles of adjuvant TMZ. Stratification factors included O6-methyl-guanine DNA methyltransferase (MGMT) promoter methylation and PS. Primary endpoint was overall survival (OS). 748 patients and 534 events were needed to detect a HR reduction of 0.775 for both concurrent and adjuvant TMZ. An interim analysis was foreseen after 219 events (41%), and required a p value of 0.0084 for rejecting the Null hypothesis of no OS difference. Results: Between Dec 2007 and Aug 2015 748 patients were randomized. On Oct 6, 2015 the interim analysis was conducted based on 221 events (median follow-up: 27 months). The analysis showed a HR reduction for OS of 0.645 (95% CI 0.450, 0.926; p= 0.0014) after adjuvant TMZ (arms iii and iv). MGMT status could be determined in 74% of patients, and was found methylated in 42% of them. MGMT methylation was prognostic for OS (HR 0.54, 95% CI 0.38, 0.77; p= 0.001), but at this stage did not predict improved outcome to adjuvant TMZ. For progression free survival (PFS), the risk adjusted HR of adjuvant TMZ was 0.586 (95% CI 0.472, 0.727; p < 0.0001). Conclusions: 12 cycles adjuvant TMZ improve OS in anaplastic glioma without 1p/19q co-deletion. Further follow-up will elucidate the role of concurrent TMZ . Molecular studies to address the impact of isocitrate dehydrogenase (IDH) mutational status and methylation profiling are ongoing. Clinical trial information: NCT00626990

Adjuvant temozolomideOS
PFS
Median% 5 yearMedian
No (n = 372)41.1 months44.1%19.0 mo
Yes (n = 373)Not reached55.9%42.8 mo