Research findings related to clinical trial development within UNITE

O6-methylguanine DNA-methyl transferase (MGMT) promoter methylation status is predictive for alkylating chemotherapy, but there are non-benefitting subgroups. The long-term update of NOA-08 compared efficacy and safety of radiotherapy (RT, n=176) and temozolomide at 7/14 days (TMZ, n=193) in patients >65 years with anaplastic astrocytoma or glioblastoma. DNA methylation patterns and copy number variations were assessed in the biomarker cohort of 104 patients and in an independent cohort of 188 patients treated with RT+TMZ-containing regimens in Heidelberg.  Wick et al. showed that MGMT promoter methylation is a strong predictive biomarker for the choice between RT and TMZ. It indicates favorable long-term outcome with initial TMZ monotherapy in patients with MGMT promoter-methylated tumors primarily in the RTK II subgroup.

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Wick A, Kessler T*, Platten M*, Meisner C, Bamberg M, Herrlinger U, Felsberg J, Weyerbrock A, Papsdorf K, Steinbach JP, Sabel M, Vesper J, Debus J, Meixensberger J, Ketter R, Hertler C, Mayer-Steinacker R, Weisang S, Bölting H, Reuss D, Reifenberger G, Sahm F*, von Deimling A*, Weller M, Wick W*; NOA-08 Study Group of the Neurooncology Working Group (NOA) of the German Cancer Society. Superiority of temozolomide over radiotherapy for elderly patients with RTK II methylation class, MGMT promoter-methylated malignant astrocytoma. Neuro Oncol. 2020 Feb 17. pii: noaa033. *UNITE Principle Investigators