Provided herein are methods for treating or preventing glioblastoma multiforme (GBM) characterized by 06-methylguanine-DNA methyltransferase (MGMT) expression and/or promoter methylation status, comprising administering an effective amount of a Dihydropyrazino-Pyrazine Compound to a patient having glioblastoma multiforme (GBM) characterized by 06-methylguanine-DNA methyltransferase (MGMT) expression and/or promoter methylation status.