Patients with newly diagnosed glioblastoma who have the best chance of responding to temozolomide can be selected via a prognostic marker that has been incorporated into a commercial assay.
The assay looks in the brain tumor for MGMT (O6-methylguanine-DNA methyltransferase), which is a key DNA repair enzyme produced by the MGMT gene. High levels of MGMT are associated with lesser response to DNA-damaging therapies such as temozolomide.
“The MGMT gene test (MDxHealth) was confirmed in the RTOG (Radiation Therapy Oncology Group) 0525 clinical trial to define prognosis for patients with newly diagnosed glioblastoma. Ongoing clinical trials have incorporated this now-validated prognostic marker to determine if subsets of patients require alternative therapies,” said Mark Gilbert, MD, of The University of Texas MD Anderson Cancer Center, Houston.
The application of a molecular risk classification to samples from the 763 patients in the RTOG 0525 trial (which evaluated 2 schedules of temozolomide) selected patients who had significant increases (P <.001) in overall survival. The approach improved on current means of prediction, by revealing an additional distinct risk group.
In particular, patients whose tumors demonstrated MGMT methylation had a median survival of 21.2 months versus 14 months without methylation (P <.001), as well as longer progression-free survival (8.7 vs 5.7, respectively; P <.001).
Treatment arm and radiation technique did not predict for survival. “This study confirmed the prognostic significance of MGMT methylation in glioblastoma,” Dr Gilbert said. The results suggest that treatment decisions based on the molecular characteristics of the tumor are not only feasible but make a clinical difference, he said.