OS01.7 MGMT promoter methylation status independently predicts progression-free survival in NRG Oncology/RTOG 9802: a phase III trial of RT vs RT + PCV in high-risk low-grade gliomas

摘要

>Background: This study sought to determine the proportion of patients with MGMT promoter methylation within NRG Oncology/RTOG 9802 and its prognostic significance in the setting of high-risk low-grade gliomas in a prospective phase III trial. >Methods: NRG Oncology/RTOG 9802 enrolled 251 eligible high-risk patients, treated with RT or RT + PCV. The MGMT-STP27 prediction model was used to calculate MGMT promoter methylation status from Illumina HM-450K data. Univariate (UMAs) and multivariate analyses (MVAs) were performed using the Cox proportional hazard model, to analyze the effect of MGMT status on progression-free survival (PFS) and overall survival (OS). Patient pre-treatment characteristics and treatment assignment were included as covariates in MVAs. >Results: Of all the eligible and randomized patients in this trial, 56 currently have MGMT status available: 43 (77%) methylated and 13 (23%) unmethylated. Between the two groups, no significant difference was observed on age and performance status at baseline. Majority of the unmethylated patients had astrocytoma dominant tumors as opposed to oligodendroglioma in the methylated group. Upon UVAs, MGMT promoter methylation was significantly correlated with better OS (HR = 2.66; p=0.01) and PFS (HR = 2.52; p=0.01). Upon MVAs, the statistical significance was maintained for PFS (HR = 3.57; p=0.001), but not OS (HR = 1.68; p=0.25). >Conclusions:MGMT promoter methylation as determined by the MGMT- STP27 model was an independent prognostic biomarker of high-risk low-grade glioma treated with radiation or radiation plus PCV for PFS. Importantly, this is the first study to validate the prognostic significance of MGMT promoter methylation in a phase III study of high-risk grade II glioma patients treated with radiation plus/minus PCV using rigorous MVAs with prospectively-collected, well-annotated clinical data. Analysis of the prognostic significance of MGMT promoter methylation relative to IDH and 1p/19q status is ongoing as well as efforts to increase sample size. FUNDING: U10CA180868, U10CA180822, and U24CA196067 (NCI). Also, R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01 (NCI), Brain Tumor Funders Collaborative Grant, and the Ohio State University CCC (all to AC).