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Clinical Trial
. 2018 Apr 9;20(5):666-673.
doi: 10.1093/neuonc/nox209.

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

Prakash Chinnaiyan  1 , Minhee Won  2 , Patrick Y Wen  3 , Amyn M Rojiani  4 , Maria Werner-Wasik  5 , Helen A Shih  6 , Lynn S Ashby  7 , Hsiang-Hsuan Michael Yu  8 , Volker W Stieber  9 , Shawn C Malone  10 , John B Fiveash  11 , Nimish A Mohile  12 , Manmeet S Ahluwalia  13 , Merideth M Wendland  14 , Philip J Stella  15 , Andrew Y Kee  16 , Minesh P Mehta  17
Affiliations
Clinical Trial

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

Prakash Chinnaiyan et al. Neuro Oncol. .

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.

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Figures

Fig. 1
Fig. 1
CONSORT diagram.
Fig. 2
Fig. 2
Principal efficacy outcomes per treatment.
See this image and copyright information in PMC

Comment in

References

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