CODEL: Phase III study of RT, RT + Temozolomide (TMZ), or TMZ for newly-diagnosed 1p/19q Codeleted Oligodendroglioma. Analysis from the initial study design.

BACKGROUND We report the analysis involving patients treated on the initial CODEL design. METHODS Adults (>18) with newly-diagnosed 1p/19q WHO grade III oligodendroglioma were randomized to RT (5940 cGy) alone (Arm A); RT with concomitant and adjuvant temozolomide (TMZ) (Arm B); or TMZ alone (Arm C). Primary endpoint was overall survival (OS), Arm A versus B. Secondary comparisons were performed for OS and progression-free survival (PFS), comparing pooled RT arms versus TMZ-alone arm. RESULTS Thirty-six patients were randomized equally. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients progressed, versus 37.5% (9/24) on the RT arms. PFS was significantly shorter in TMZ-alone patients compared to RT-treated patients (HR=3.12; 95% CI: 1.26, 7.69; p=0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) on the RT Arms. OS did not statistically differ between arms (comparison underpowered). After adjustment for IDH status (mutated/wildtype) in a Cox regression model utilizing IDH and RT treatment status as co-variables (Arm C vs pooled Arms A+B), PFS remained shorter for patients not receiving RT, (HR= 3.33; 95% CI: 1.31, 8.45; p=0.011), but not OS ((HR = 2.78; 95% CI 0.58, 13.22, p=0.20). Grade 3+ adverse events occurred in 25%, 42% and 33% of patients (Arms A, B, and C). There were no differences between Arms in neurocognitive decline comparing baseline to 3 months. CONCLUSIONS TMZ-alone patients experienced significantly shorter PFS than patients treated on the RT Arms. The ongoing CODEL trial has been redesigned to compare RT+PCV versus RT+TMZ.