Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: Results of nrg oncology RTOG 9813

Susan Chang, Peixin Zhang, J. Gregory Cairncross, Mark R. Gilbert, Jean Paul Bahary, Carol A. Dolinskas, Arnab Chakravarti, Kenneth D. Aldape, Erica H. Bell, David Schiff, Kurt Jaeckle, Paul D. Brown, Geoffrey R. Barger, Maria Werner-Wasik, Helen Shih, David Brachman, Marta Penas-Prado, H. Ian Robins, Karl Belanger, Christopher SchultzGrant Hunter, Minesh Mehta

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Abstract

Background: The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated with radiotherapy (RT) and either temozolomide (TMZ) or a nitrosourea (NU). Secondary endpoints were time to tumor progression (TTP), toxicity, and the effect of IDH1 mutation status on clinical outcome. Methods: Eligible patients with centrally reviewed, histologically confirmed, newly diagnosed AA were randomized to receive either RT+TMZ (n = 97) or RT+NU (n = 99). The study closed early because the target accrual rate was not met. Results: Median follow-up time for patients still alive was 10.1 years (1.9.12.6 y); 66% of the patients died. Median survival time was 3.9 years in the RT/TMZ arm (95% CI, 3.0.7.0) and 3.8 years in the RT/NU arm (95% CI, 2.2.7.0), corresponding to a hazard ratio (HR) of 0.94 (P =.36; 95% CI, 0.67.1.32). The differences in progression-free survival (PFS) and TTP between the 2 arms were not statistically significant. Patients in the RT+NU arm experienced more grade.3 toxicity (75.8% vs 47.9%, P <.001), mainly related to myelosuppression. Of the 196 patients, 111 were tested for IDH1-R132H status (60 RT+TMZ and 51 RT+NU). Fifty-four patients were IDH negative and 49 were IDH positive with a better OS in IDH-positive patients (median survival time 7.9 vs 2.8 y; P =.004, HR = 0.50; 95% CI, 0.31.0.81). Conclusions: RT+TMZ did not appear to significantly improve OS or TTP for AA compared with RT+ NU. RT+TMZ was better tolerated. IDH1-R132H mutation was associated with longer survival.

Original languageEnglish (US)
Pages (from-to)252-258
Number of pages7
JournalNeuro-Oncology
Volume19
Issue number2
DOIs
StatePublished - Jan 1 2017

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temozolomide
Astrocytoma
Radiotherapy
Radiation
Survival
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Chang, Susan ; Zhang, Peixin ; Cairncross, J. Gregory ; Gilbert, Mark R. ; Bahary, Jean Paul ; Dolinskas, Carol A. ; Chakravarti, Arnab ; Aldape, Kenneth D. ; Bell, Erica H. ; Schiff, David ; Jaeckle, Kurt ; Brown, Paul D. ; Barger, Geoffrey R. ; Werner-Wasik, Maria ; Shih, Helen ; Brachman, David ; Penas-Prado, Marta ; Robins, H. Ian ; Belanger, Karl ; Schultz, Christopher ; Hunter, Grant ; Mehta, Minesh. / Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma : Results of nrg oncology RTOG 9813. In: Neuro-Oncology. 2017 ; Vol. 19, No. 2. pp. 252-258.
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abstract = "Background: The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated with radiotherapy (RT) and either temozolomide (TMZ) or a nitrosourea (NU). Secondary endpoints were time to tumor progression (TTP), toxicity, and the effect of IDH1 mutation status on clinical outcome. Methods: Eligible patients with centrally reviewed, histologically confirmed, newly diagnosed AA were randomized to receive either RT+TMZ (n = 97) or RT+NU (n = 99). The study closed early because the target accrual rate was not met. Results: Median follow-up time for patients still alive was 10.1 years (1.9.12.6 y); 66{\%} of the patients died. Median survival time was 3.9 years in the RT/TMZ arm (95{\%} CI, 3.0.7.0) and 3.8 years in the RT/NU arm (95{\%} CI, 2.2.7.0), corresponding to a hazard ratio (HR) of 0.94 (P =.36; 95{\%} CI, 0.67.1.32). The differences in progression-free survival (PFS) and TTP between the 2 arms were not statistically significant. Patients in the RT+NU arm experienced more grade.3 toxicity (75.8{\%} vs 47.9{\%}, P <.001), mainly related to myelosuppression. Of the 196 patients, 111 were tested for IDH1-R132H status (60 RT+TMZ and 51 RT+NU). Fifty-four patients were IDH negative and 49 were IDH positive with a better OS in IDH-positive patients (median survival time 7.9 vs 2.8 y; P =.004, HR = 0.50; 95{\%} CI, 0.31.0.81). Conclusions: RT+TMZ did not appear to significantly improve OS or TTP for AA compared with RT+ NU. RT+TMZ was better tolerated. IDH1-R132H mutation was associated with longer survival.",
author = "Susan Chang and Peixin Zhang and Cairncross, {J. Gregory} and Gilbert, {Mark R.} and Bahary, {Jean Paul} and Dolinskas, {Carol A.} and Arnab Chakravarti and Aldape, {Kenneth D.} and Bell, {Erica H.} and David Schiff and Kurt Jaeckle and Brown, {Paul D.} and Barger, {Geoffrey R.} and Maria Werner-Wasik and Helen Shih and David Brachman and Marta Penas-Prado and Robins, {H. Ian} and Karl Belanger and Christopher Schultz and Grant Hunter and Minesh Mehta",
year = "2017",
month = "1",
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doi = "10.1093/neuonc/now23",
language = "English (US)",
volume = "19",
pages = "252--258",
journal = "Neuro-Oncology",
issn = "1522-8517",
publisher = "Oxford University Press",
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}

Chang, S, Zhang, P, Cairncross, JG, Gilbert, MR, Bahary, JP, Dolinskas, CA, Chakravarti, A, Aldape, KD, Bell, EH, Schiff, D, Jaeckle, K, Brown, PD, Barger, GR, Werner-Wasik, M, Shih, H, Brachman, D, Penas-Prado, M, Robins, HI, Belanger, K, Schultz, C, Hunter, G & Mehta, M 2017, 'Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: Results of nrg oncology RTOG 9813', Neuro-Oncology, vol. 19, no. 2, pp. 252-258. https://doi.org/10.1093/neuonc/now23

Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma : Results of nrg oncology RTOG 9813. / Chang, Susan; Zhang, Peixin; Cairncross, J. Gregory; Gilbert, Mark R.; Bahary, Jean Paul; Dolinskas, Carol A.; Chakravarti, Arnab; Aldape, Kenneth D.; Bell, Erica H.; Schiff, David; Jaeckle, Kurt; Brown, Paul D.; Barger, Geoffrey R.; Werner-Wasik, Maria; Shih, Helen; Brachman, David; Penas-Prado, Marta; Robins, H. Ian; Belanger, Karl; Schultz, Christopher; Hunter, Grant; Mehta, Minesh.

In: Neuro-Oncology, Vol. 19, No. 2, 01.01.2017, p. 252-258.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma

T2 - Results of nrg oncology RTOG 9813

AU - Chang, Susan

AU - Zhang, Peixin

AU - Cairncross, J. Gregory

AU - Gilbert, Mark R.

AU - Bahary, Jean Paul

AU - Dolinskas, Carol A.

AU - Chakravarti, Arnab

AU - Aldape, Kenneth D.

AU - Bell, Erica H.

AU - Schiff, David

AU - Jaeckle, Kurt

AU - Brown, Paul D.

AU - Barger, Geoffrey R.

AU - Werner-Wasik, Maria

AU - Shih, Helen

AU - Brachman, David

AU - Penas-Prado, Marta

AU - Robins, H. Ian

AU - Belanger, Karl

AU - Schultz, Christopher

AU - Hunter, Grant

AU - Mehta, Minesh

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background: The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated with radiotherapy (RT) and either temozolomide (TMZ) or a nitrosourea (NU). Secondary endpoints were time to tumor progression (TTP), toxicity, and the effect of IDH1 mutation status on clinical outcome. Methods: Eligible patients with centrally reviewed, histologically confirmed, newly diagnosed AA were randomized to receive either RT+TMZ (n = 97) or RT+NU (n = 99). The study closed early because the target accrual rate was not met. Results: Median follow-up time for patients still alive was 10.1 years (1.9.12.6 y); 66% of the patients died. Median survival time was 3.9 years in the RT/TMZ arm (95% CI, 3.0.7.0) and 3.8 years in the RT/NU arm (95% CI, 2.2.7.0), corresponding to a hazard ratio (HR) of 0.94 (P =.36; 95% CI, 0.67.1.32). The differences in progression-free survival (PFS) and TTP between the 2 arms were not statistically significant. Patients in the RT+NU arm experienced more grade.3 toxicity (75.8% vs 47.9%, P <.001), mainly related to myelosuppression. Of the 196 patients, 111 were tested for IDH1-R132H status (60 RT+TMZ and 51 RT+NU). Fifty-four patients were IDH negative and 49 were IDH positive with a better OS in IDH-positive patients (median survival time 7.9 vs 2.8 y; P =.004, HR = 0.50; 95% CI, 0.31.0.81). Conclusions: RT+TMZ did not appear to significantly improve OS or TTP for AA compared with RT+ NU. RT+TMZ was better tolerated. IDH1-R132H mutation was associated with longer survival.

AB - Background: The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated with radiotherapy (RT) and either temozolomide (TMZ) or a nitrosourea (NU). Secondary endpoints were time to tumor progression (TTP), toxicity, and the effect of IDH1 mutation status on clinical outcome. Methods: Eligible patients with centrally reviewed, histologically confirmed, newly diagnosed AA were randomized to receive either RT+TMZ (n = 97) or RT+NU (n = 99). The study closed early because the target accrual rate was not met. Results: Median follow-up time for patients still alive was 10.1 years (1.9.12.6 y); 66% of the patients died. Median survival time was 3.9 years in the RT/TMZ arm (95% CI, 3.0.7.0) and 3.8 years in the RT/NU arm (95% CI, 2.2.7.0), corresponding to a hazard ratio (HR) of 0.94 (P =.36; 95% CI, 0.67.1.32). The differences in progression-free survival (PFS) and TTP between the 2 arms were not statistically significant. Patients in the RT+NU arm experienced more grade.3 toxicity (75.8% vs 47.9%, P <.001), mainly related to myelosuppression. Of the 196 patients, 111 were tested for IDH1-R132H status (60 RT+TMZ and 51 RT+NU). Fifty-four patients were IDH negative and 49 were IDH positive with a better OS in IDH-positive patients (median survival time 7.9 vs 2.8 y; P =.004, HR = 0.50; 95% CI, 0.31.0.81). Conclusions: RT+TMZ did not appear to significantly improve OS or TTP for AA compared with RT+ NU. RT+TMZ was better tolerated. IDH1-R132H mutation was associated with longer survival.

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