Susan Chang1, Peixin Zhang2, J Gregory Cairncross3, Mark R Gilbert4, Jean-Paul Bahary5, Carol A Dolinskas6, Arnab Chakravarti7, Kenneth D Aldape8, Erica H Bell9, David Schiff10, Kurt Jaeckle11, Paul D Brown4, Geoffrey R Barger12, Maria Werner-Wasik13, Helen Shih14, David Brachman15, Marta Penas-Prado4, H Ian Robins16, Karl Belanger5, Christopher Schultz17, Grant Hunter18, Minesh Mehta19. 1. University of California San Francisco, San Francisco, California, USA. 2. NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania, USA. 3. University of Calgary, Calgary, Canada. 4. University of Texas-MD Anderson Cancer Center, Houston, Texas, USA. 5. Centre Hospitalier de l`Université de Montréal-Notre Dame, Montréal, Canada. 6. University of Pennsylvania, Philadelphia, Pennsylvania, USA. 7. Department of Radiation Oncology, The Ohio State University, Columbus, OH, USA. 8. MacFeeters Hamilton Center for Neuro-Oncology, Toronto, Canada. 9. The Ohio State University Medical Center, Columbus, Ohio, USA. 10. University of Virginia, Charlottesville, Virginia, USA. 11. Mayo Clinic, Jacksonville, Florida, USA. 12. Wayne State University, Detroit, Michigan, USA. 13. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA. 14. Massachusetts General Hospital, Boston, Massachusetts, USA. 15. Arizona Oncology Services Foundation, Phoenix, Arizona, USA. 16. University of Wisconsin Hospital, Madison, Wisconsin, USA. 17. Medical College of Wisconsin, Milwaukee, Wisconsin, USA. 18. Intermountain Medical Center, Murray, Utah, USA. 19. University of Maryland Medical Systems, Baltimore, Maryland, USA.
Abstract
Background: The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated withradiotherapy (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.
RCT Entities:
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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