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 mammalian target of rapamycin (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 a significant increase in both grade 4 toxicities, including lymphopenia and thrombocytopenia, and treatment-related deaths. There was no significant difference in PFS between patients randomized to everolimus compared with control (median PFS time: 8.2 vs 10.2 mo, respectively; P = 0.79). OS for patients randomized to receive everolimus was inferior to that for control patients (median survival time: 16.5 vs 21.2 mo, respectively; P = 0.008). A similar trend was observed in both O6-methylguanine-DNA-methyltransferase promoter hypermethylated and unmethylated tumors.

Conclusion:

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

• Authors: Prakash Chinnaiyan, Minhee Won, Patrick Y Wen, Amyn M Rojiani, Maria Werner-Wasik, Helen A Shih, Lynn S Ashby, Hsiang-Hsuan Michael Yu, Volker W Stieber, Shawn C Malone, John B Fiveash, Nimish A Mohile, Manmeet S Ahluwalia, Merideth M Wendland, Philip J Stella, Andrew Y Kee, Minesh P Mehta
• Journal: Neuro-oncology (Neuro Oncol) Vol. 20 Issue 5 Pg. 666-673 (04 09 2018) ISSN: 1523-5866 [Electronic] England
• PMID: 29126203 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Dacarbazine
• Everolimus
• Temozolomide

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Brain Neoplasms (pathology, therapy)
• Chemoradiotherapy (mortality)
• Dacarbazine (administration & dosage)
• Everolimus (administration & dosage)
• Female
• Follow-Up Studies
• Glioblastoma (pathology, therapy)
• Humans
• Male
• Middle Aged
• Prognosis
• Survival Rate
• Temozolomide (administration & dosage)
• Young Adult