Data from <i>MGMT</i> Promoter Methylation Predicts Overall Survival after Chemotherapy for 1p/19q-Codeleted Gliomas

Abstract

<div>AbstractPurpose:<p>While <i>MGMT</i> promoter methylation (m<i>MGMT</i>) is predictive of response to alkylating chemotherapy and guides treatment decisions in glioblastoma, its role in grade 2 and 3 glioma remains unclear. Recent data suggest that m<i>MGMT</i> is prognostic of progression-free survival in 1p/19q-codeleted oligodendrogliomas, but an effect on overall survival (OS) has not been demonstrated.</p>Experimental Design:<p>We identified patients with newly diagnosed 1p/19q-codeleted gliomas and known <i>MGMT</i> promoter status in the National Cancer Database from 2010 to 2019. Multivariable Cox proportional hazards regression modeling was used to assess the effect of m<i>MGMT</i> on OS after adjusting for age, sex, race, comorbidity, grade, extent of resection, chemotherapy, and radiotherapy.</p>Results:<p>We identified 1,297 eligible patients, 938 (72.3%) of whom received chemotherapy in their initial course of treatment. The <i>MGMT</i> promoter was methylated in 1,009 (77.8%) patients. Unmethylated <i>MGMT</i> (u<i>MGMT</i>) was associated with worse survival compared with m<i>MGMT</i> [70% {95% confidence interval (CI), 64%–77%} vs. 81% (95% CI, 78%–85%); <i>P</i> < 0.001; adjusted HR (aHR), 2.35 (95% CI, 1.77–3.14)]. u<i>MGMT</i> was associated with worse survival in patients who received chemotherapy [63% (95% CI, 55–73%) vs. 80% (95% CI, 76%–84%); <i>P</i> < 0.001; aHR, 2.61 (95% CI, 1.89–3.60)] but not in patients who did not receive chemotherapy [<i>P</i> = 0.38; HR, 1.31 (95% CI, 0.71–2.42)]. Similar results were observed regardless of World Health Organization grade and after single- or multiagent chemotherapy.</p>Conclusions:<p>Our study demonstrates an association between m<i>MGMT</i> and OS in 1p/19q-codeleted gliomas. <i>MGMT</i> promoter status should be considered as a stratification factor in future clinical trials of 1p/19q-codeleted gliomas that use OS as an endpoint.</p></div>