CODEL: phase III study of RT, RT + TMZ, or TMZ for newly diagnosed 1p/19q codeleted oligodendroglioma. Analysis from the initial study design

Kurt A. Jaeckle, Karla V. Ballman, Martin van den Bent, Caterina Giannini, Evanthia Galanis, Paul D. Brown, Robert B. Jenkins, J. Gregory Cairncross, Wolfgang Wick, Michael Weller, Kenneth D. Aldape, Jesse G. Dixon, S. Keith Anderson, Jane H. Cerhan, Jeffrey S. Wefel, Martin Klein, Stuart A. Grossman, David Schiff, Jeffrey J. Raizer, Frederick DhermainDonald G. Nordstrom, Patrick J. Flynn, Michael A. Vogelbaum

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: We report the analysis involving patients treated on the initial CODEL design. METHODS: Adults (>18) with newly diagnosed 1p/19q World Health Organization (WHO) grade III oligodendroglioma were randomized to radiotherapy (RT; 5940 centigray ) 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 with RT patients (hazard ratio [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 isocitrate dehydrogenase (IDH) status (mutated/wildtype) in a Cox regression model utilizing IDH and RT treatment status as covariables (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.

Original languageEnglish (US)
Pages (from-to)457-467
Number of pages11
JournalNeuro-oncology
Volume23
Issue number3
DOIs
StatePublished - Mar 25 2021

Keywords

  • 1p/19q
  • CODEL
  • N0577
  • codeleted
  • oligodendroglioma

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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