ACTR-11. SECOND INTERIM AND 1ST MOLECULAR ANALYSIS OF THE EORTC RANDOMIZED PHASE III INTERGROUP CATNON TRIAL ON CONCURRENT AND ADJUVANT TEMOZOLOMIDE IN ANAPLASTIC GLIOMA WITHOUT 1p/19q CODELETION

Abstract

Abstract 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 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. Isocitrate dehydrogenase 1 and 2 (IDH) mutation (mt) status was assessed with a glioma targeted next generation sequencing panel. At the time of molecular analysis, a 3rd database lock was done. RESULTS At the 2nd IDMC (median follow-up 56 months, 356 events observed) the hazard ratio (HR) for OS adjusted for stratification factors after concTMZ was 0.968 (99.1% CI 0.73, 1.28. An IDHmt was found in 368 of 528 assessed cases (70%). After median follow-up of 67 months and with 367 events observed 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. IDHmt was predictive of benefit from adjTMZ (IDHmt HR: 0.46, 95% CI 0.32, 0.67; IDHwt: HR 1.03, 95% CI 0.73, 1.44; interaction test p = 0.002) and from concTMZ (HR(IDHmt HR: 0.63, 95% CI 0.43, 0.91; IDHwt: HR 1.16, 95% CI 0.83, 1.63; interaction test p = 0.017). MGMTmeth was found in 401 of 478 assessed cases (69%), interaction tests for concTMZ and adjTMZ did not reach statistical significance. CONCLUSIONS In IDHmt tumors adjuvant and concurrent temozolomide improves survival, no effect was observed in IDHwt tumors. Further follow-up and molecular analyses are required for mature analyses.