A randomized phase II study of everolimus in combination with chemoradiation in newly diagnosed glioblastoma: Results of NRG Oncology RTOG 0913

Abstract

Background

This Phase II study was designed to determine the efficacy of the mTOR inhibitor everolimus administered daily with conventional radiation therapy and chemotherapy in patients with newly diagnosed glioblastoma.

Methods

Patients were randomized to radiation therapy with concurrent and adjuvant temozolomide with or without daily everolimus (10 mg). The primary endpoint was progression-free survival (PFS) and the secondary endpoints were overall survival (OS) and treatment-related toxicities.

Results

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

Conclusion

Combining everolimus with conventional chemoradiation leads to increased treatment-related toxicities and did not improve PFS in patients with newly diagnosed glioblastoma. Although the MST in patients receiving everolimus was comparable to contemporary studies, it was inferior to the control in this randomized study.