ATCT-12: RESULTS OF NRG ONCOLOGY/RTOG 9813- A PHASE III RANDOMIZED STUDY OF RADIATION THERAPY (RT) AND TEMOZOLOMIDE (TMZ) VERSUS RT AND NITROSOUREA (NU) THERAPY FOR ANAPLASTIC ASTROCYTOMA (AA)

BACKGROUND: The primary objective of this study was to compare overall survival (OS) of patients with AA treated with RT and either TMZ or NU. Secondary endpoints: time to tumor progression (TTP), toxicities of the regimens and molecular analyses. METHODS: Eligibility criteria: age ≥18 years; central review of AA; KPS ≥60. Patients were randomized 1:1 to RT 59.4 Gy with TMZ versus NU (BCNU or CCNU). An estimated increase from 3 to 4.5 years on the median survival time (MST) would require a sample size of 216 patients per arm (power = 90% with a one-sided alpha = 0.05). RESULTS: Because accrual goals were not met, the trial was closed in 2007. From 2002-2007, 196 eligible patients were randomized, 97 (RT + TMZ) and 99 (RT + NU). Stratification factors were balanced between the 2 arms. 65% of patients have died at the time of this report. Median follow-up time for patients still alive was 9.1 years (1.9-11.6 years). There was no difference in OS between the RT + TMZ and the RT + NU arm (MST 3.9 versus 3.8 years; p-value = 0.37). The differences in PFS and TTP between the 2 arms were not statistically significant. The RT + NU arm had a significantly higher rate of worse overall grade ≥3 toxicity (75.8% versus 47.9%; p-value < .001), related to bone marrow toxicity. Of the 196 patients, 111 were tested for IDH status, 60 (RT + TMZ) and 51 (RT + NU). 54 patients were IDH negative and 49 were IDH positive with a better OS in IDH positive patients (MST 7.9 versus 2.8 years; p-value = 0.006, HR = 0.51; 95% CI: 0.31-0.83). CONCLUSIONS: RT + TMZ did not appear to significantly improve OS or TTP for AA compared with RT+ NU. RT + TMZ was better tolerated. IDH mutation was associated with better survival outcome. Clinical trial information: NCT00004259. Supported by National Cancer Institute grants U10CA21661, U10CA180868, U10CA180822 and U10CA37422 and Merck & Co.