Chinnaiyan P, et al. - Researchers designed this phase II study to assess the efficacy of the mTOR inhibitor everolimus given daily with conventional radiation therapy and chemotherapy in patients with newly diagnosed glioblastoma. Observations revealed increased treatment-related toxicities and no improvement in progression-free survival (PFS) on combining everolimus with conventional chemoradiation in these patients. In this randomized study, median survival time (MST) in patients receiving everolimus was inferior to the control, although it was comparable to contemporary studies.

Methods

• Researchers randomized patients to radiation therapy with concurrent and adjuvant temozolomide with or without daily everolimus (10 mg).
• They primarily assessed progression-free survival (PFS).
• Secondarily, they assessed overall survival (OS) and treatment-related toxicities.

Results

• For this study, total of 171 patients were randomized and deemed eligible.
• A significant increase in Grade 4 toxicities including lymphopenia and thrombocytopenia, and treatment-related deaths were evident among patients receiving everolimus.
• Patients randomized to everolimus, compared to control, indicated no significant difference in PFS (median PFS time: 8.2 vs. 10.2 months, respectively; p=0.79).
• Patients randomized to receive everolimus indicated inferior OS in comparison to the control patients (median survival time (MST): 16.5 vs. 21.2 months, respectively; p=0.008).
• They observed a similar trend in both 06-methylguanine-DNA-methyltransferase (MGMT) promoter hypermethylated and unmethylated tumors.