CODEL (Alliance-N0577; EORTC-26081/22086; NRG-1071; NCIC-CEC-2): Phase III Randomized Study of RT vs. RT+TMZ vs. TMZ for Newly Diagnosed 1p/19q-Codeleted Anaplastic Oligodendroglial Tumors. Analysis of Patients Treated on the Original Protocol Design (PL02.005)

Abstract

OBJECTIVE: To define treatment for newly diagnosed 1p/19q-codeleted anaplastic glioma patients(pts). BACKGROUND: Following EORTC 26951/RTOG 9402 reports, the original CODEL trial, which contained an RT-alone control arm, was closed. The study reopened later with a RT+PCV control arm. We performed analysis of the initial pts randomized per the original CODEL design. METHODS: Adults (18+) pts with newly-diagnosed 1p/19q codeleted WHO grade III gliomas were randomized to RT (5940 cGy) alone (Arm A); vs. RT+TMZ (75mg/M2/D; 150-200mg/M2, D1-5 q28D X6-12 (Arm B); vs. TMZ alone (150-200mg/M2, D1-5q28D X12 (Arm C). Stratification included age (+/-50), North America vs EORTC, and ECOG status (0-1 vs. 2). Primary endpoint was overall survival. PFS was compared (logrank test, Arm C vs. Arms A+B pooled). RESULTS: 36 pts (N.A.-53[percnt], EORTC-47[percnt]) were randomized (Arm A-12; Arm B-12; Arm C-12), balanced for age, ECOG status, and resection extent. Grade 3+ toxicity occurred in 25[percnt], 42[percnt] and 33[percnt] pts (Arms A, B and C, respectively). Two RT-arm pts withdrew due to toxicity (A-1; B-1). All treatment cycles were completed in 92[percnt] (Arm A), 83[percnt] (Arm B) and 58[percnt] (Arm C) pts. Progression during treatment occurred in 5/12 (42[percnt]) TMZ-alone pts, vs. 0/24 (0[percnt]) on RT arms. With median follow-up of 3.5 yrs, 7/12(58[percnt]) TMZ-alone pts progressed, vs. 3/24(12.5[percnt]) RT-Arm pts (p = 0.007). Death from disease progression occurred in 33[percnt] (4/12) TMZ-alone pts vs. 4[percnt] (1/24) RT-Arm pts (A-0; B-1;p = 0.03). Median PFS was shorter in TMZ-alone pts (2.5 yrs vs. not reached for RT-Arm pts; HR=7.0, p<=0.001); OS was shorter (HR=9.2, p=0.048). CONCLUSIONS: TMZ-alone treated pts experienced shorter PFS, OS, and time to death from progression vs. those treated with RT or RT+TMZ. Accordingly, the Alliance DSMC recommended closure of Arm C. CODEL has reopened as a two-arm comparison of RT+adjuvant PCV vs. RT+concomitant/adjuvant TMZ. (Support: U10CA180821;U10CA180882)

Disclosure: Dr. Jaeckle has received personal compensation for activities with Bristol Meyers Squibb and Orbus Therapeutics. Dr. Vogelbaum has received personal compensation for activities with NeuralStem. Dr. Ballman has nothing to disclose. Dr. Anderson has nothing to disclose. Dr. Giannini has nothing to disclose. Dr. Aldape has received personal compensation for activities with Merck as a consultant. Dr. Cerhan has nothing to disclose. Dr. Wefel has received personal compensation for activities with Roche, Genentech, and Eli Lilly. Dr. Nordstrom has nothing to disclose. Dr. Jenkins has nothing to disclose. Dr. Klein has nothing to disclose. Dr. Raizer has received personal compensation for activities with Genentech, Inc., Abbvie, Stemline, Foundation medicine, Novocure, Proximagene, and BMS as a speaker and/or advisory board member. Dr. Van Den Bent has received personal compensation for activities with Roche Diagnostics Corporation, AbbVie, Actelion, Celldex, Amgen, Novartis, Novocure Merk Ag, and BMS as a consultant. Dr. Van Den has received personal compensation in an editorial ca Dr. Wick has received personal compensation for activities with Roche Diagnostics Corporation and Merck Sharp & Dohme Ltd. Dr. Flynn has nothing to disclose. Dr. Dhermain has nothing to disclose. Dr. Cairncross has nothing to disclose. Dr. Galanis has nothing to disclose. Dr. Brown has nothing to disclose.