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.

Abstract

LBA2000 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. [Table: see text]