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 Dhermain; Donald G Nordstrom; Patrick J Flynn; Michael A Vogelbaum

doi:10.1093/neuonc/noaa168

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

Neuro Oncol. 2021 Mar 25;23(3):457-467. doi: 10.1093/neuonc/noaa168.

Authors

Kurt A Jaeckle¹, Karla V Ballman², Martin van den Bent³, Caterina Giannini⁴, Evanthia Galanis⁴, Paul D Brown⁴, Robert B Jenkins⁴, J Gregory Cairncross⁵, Wolfgang Wick⁶, Michael Weller⁷, Kenneth D Aldape⁸, Jesse G Dixon⁹, S Keith Anderson⁹, Jane H Cerhan¹⁰, Jeffrey S Wefel¹¹, Martin Klein¹², Stuart A Grossman¹³, David Schiff¹⁴, Jeffrey J Raizer¹⁵, Frederick Dhermain¹⁶, Donald G Nordstrom¹⁷, Patrick J Flynn¹⁸, Michael A Vogelbaum¹⁹

Affiliations

¹ Department of Neurology, Mayo Clinic Florida, Jacksonville, Florida, USA.
² Alliance Statistics and Data Center, Weill Cornell Medicine, New York, New York, USA.
³ Brain Tumor Center, Erasmus MC Cancer Center, Erasmus University Medical Center, Rotterdam, Netherlands.
⁴ Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
⁵ Department of Clinical Neurosciences, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.
⁶ Neurologische Klinik, University of Heidelberg, Heidelberg, Germany.
⁷ Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
⁸ Department of Neuropathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁹ Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota, USA.
¹⁰ Departments of Psychiatry and Psychology, Houston, Texas, USA.
¹¹ Departments of Neuro-Oncology and Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
¹² Department of Medical Psychology, VU University Medical Center, Amsterdam, Netherlands.
¹³ Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.
¹⁴ Department of Neurology, University of Virginia, Charlottesville, Virginia, USA.
¹⁵ Department of Neurology, Northwestern University, Chicago, Illinois, USA.
¹⁶ Department of Radiation Therapy, Gustave Roussy Cancer Institute, Villejuif, France.
¹⁷ Medical Oncology, France Abben Cancer Center, Spencer, Iowa, USA.
¹⁸ Medical Oncology, Minnesota Oncology, Northfield, Minnesota, USA.
¹⁹ Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio, USA.

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.

Keywords: 1p/19q; CODEL; N0577; codeleted; oligodendroglioma.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, N.I.H., Extramural

MeSH terms

Adult
Brain Neoplasms* / drug therapy
Brain Neoplasms* / genetics
Humans
Isocitrate Dehydrogenase / genetics
Oligodendroglioma* / drug therapy
Oligodendroglioma* / genetics
Progression-Free Survival
Temozolomide / therapeutic use

Substances

Isocitrate Dehydrogenase
Temozolomide

Abstract

Publication types

MeSH terms

Substances

Grants and funding