A randomized phase II study of everolimus in combination with chemoradiation in newly diagnosed glioblastoma

Results of NRG Oncology RTOG 0913

Prakash Chinnaiyan, Minhee Won, Patrick Y. Wen, Amyn Mohammed 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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 O 6-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.

Original languageEnglish (US)
Pages (from-to)666-673
Number of pages8
JournalNeuro-Oncology
Volume20
Issue number5
DOIs
StatePublished - Apr 9 2018

Fingerprint

Glioblastoma
Disease-Free Survival
Survival
temozolomide
O(6)-Methylguanine-DNA Methyltransferase
Radiotherapy
Everolimus
Lymphopenia
Sirolimus
Thrombocytopenia
Therapeutics
Drug Therapy

Keywords

  • everolimus
  • glioblastoma
  • mTOR inhibition
  • phase II trial
  • radiation sensitizer

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

A randomized phase II study of everolimus in combination with chemoradiation in newly diagnosed glioblastoma : Results of NRG Oncology RTOG 0913. / Chinnaiyan, Prakash; Won, Minhee; Wen, Patrick Y.; Rojiani, Amyn Mohammed; Werner-Wasik, Maria; Shih, Helen A.; Ashby, Lynn S.; Michael Yu, Hsiang Hsuan; Stieber, Volker W.; Malone, Shawn C.; Fiveash, John B.; Mohile, Nimish A.; Ahluwalia, Manmeet S.; Wendland, Merideth M.; Stella, Philip J.; Kee, Andrew Y.; Mehta, Minesh P.

In: Neuro-Oncology, Vol. 20, No. 5, 09.04.2018, p. 666-673.

Research output: Contribution to journalArticle

Chinnaiyan, P, Won, M, Wen, PY, Rojiani, AM, Werner-Wasik, M, Shih, HA, Ashby, LS, Michael Yu, HH, Stieber, VW, Malone, SC, Fiveash, JB, Mohile, NA, Ahluwalia, MS, Wendland, MM, Stella, PJ, Kee, AY & Mehta, MP 2018, 'A randomized phase II study of everolimus in combination with chemoradiation in newly diagnosed glioblastoma: Results of NRG Oncology RTOG 0913', Neuro-Oncology, vol. 20, no. 5, pp. 666-673. https://doi.org/10.1093/neuonc/nox209
Chinnaiyan, Prakash ; Won, Minhee ; Wen, Patrick Y. ; Rojiani, Amyn Mohammed ; Werner-Wasik, Maria ; Shih, Helen A. ; Ashby, Lynn S. ; Michael Yu, Hsiang Hsuan ; Stieber, Volker W. ; Malone, Shawn C. ; Fiveash, John B. ; Mohile, Nimish A. ; Ahluwalia, Manmeet S. ; Wendland, Merideth M. ; Stella, Philip J. ; Kee, Andrew Y. ; Mehta, Minesh P. / A randomized phase II study of everolimus in combination with chemoradiation in newly diagnosed glioblastoma : Results of NRG Oncology RTOG 0913. In: Neuro-Oncology. 2018 ; Vol. 20, No. 5. pp. 666-673.
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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 O 6-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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AU - Wen, Patrick Y.

AU - Rojiani, Amyn Mohammed

AU - Werner-Wasik, Maria

AU - Shih, Helen A.

AU - Ashby, Lynn S.

AU - Michael Yu, Hsiang Hsuan

AU - Stieber, Volker W.

AU - Malone, Shawn C.

AU - Fiveash, John B.

AU - Mohile, Nimish A.

AU - Ahluwalia, Manmeet S.

AU - Wendland, Merideth M.

AU - Stella, Philip J.

AU - Kee, Andrew Y.

AU - Mehta, Minesh P.

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N2 - 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 O 6-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.

AB - 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 O 6-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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