Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813

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 IDH1R132H 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.