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Initial radiotherapy, chemotherapy produced equivalent results with anaplastic glioma
Data may fail to help guide treatment decisions.
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Chemotherapy and radiation produced similar outcomes for patients with anaplastic gliomas, which led researchers of the NOA-04 phase-3 trial to conclude that either therapy is appropriate, but patients should not undergo both types of treatment.
Writing in an accompany editorial, Lisa M. DeAngelis, MD, chair of neurology at Memorial-Sloan Kettering Cancer Center, said the results of the phase-3 trial could have been predicted from the study’s design, and “the data fail to guide future treatment decisions for these patients.”
From June 1999 to February 2005, Wolfgang Wick, MD, laboratory of molecular neurooncology, department of general neurology, Hertie Institute for Clinical Brain Research, and colleagues recruited 318 adult patients with stage III anaplastic gliomas who had never received systemic chemotherapy or radiotherapy to the brain. The intent-to-treat population was 274.
Patients were randomly assigned in a 2:1:1 ratio to radiotherapy (n=160) or chemotherapy with temozolomide (Temodar, Schering; n=78) or procarbazine, lomustine and vincristine (n=80). Patients assigned radiotherapy were transferred to chemotherapy upon relapse, and those assigned chemotherapy were assigned radiotherapy when they relapsed.
One hundred and seventeen patients had reached time-to-treatment failure at a maximum follow-up of 54 months. Median time-to-treatment failure was 42.7 months in the radiotherapy first arm and 43.8 months in the chemotherapy first arms. Unadjusted HR for time-to-treatment failure in the radiotherapy first arm vs. the chemotherapy groups was 1.2 (95% CI, 0.8-1.8).
Median PFS was 30.6 months for the radiotherapy first arm and 31.9 months for the chemotherapy arms. Wick and colleagues wrote that there was no difference in median OS observed, and no difference in PFS between the two chemotherapy groups.
“Unfortunately, the interpretation of this study is markedly compromised by its design. The authors do not describe their hypothesis for the study or how such a complicated trial structure would address their question,” DeAngelis wrote. “In the absence of pre-existing data suggesting the sequence of therapeutic modalities should affect outcome, the study was destined to show equivalence between the two treatment arms. Only if treatment sequence affected tumor progression after all therapy was administered could there be a difference between the study arms.”
DeAngelis said the researchers demonstrated the importance of molecular markers in anaplastic gliomas. The researchers showed that IDH1 mutation was associated with improved PFS regardless of treatment arm, histology, 1p/19q status or MGMT promoter methylation.
“In fact, in the multivariate model, IDH1 mutation conferred a stronger risk reduction (HR=0.47; 95% CI, 0.3-0.77) than 1p/19q codeletion (HR=0.47; 95% CI, 0.3-0.83), MGMT promoter methylation (HR=0.59; 95% CI, 0.37-1.1), or histology (HR=0.63; 95% CI, 0.38-1.0),” the researchers wrote.
DeAngelis said the results of this study do not demonstrate the “best therapeutic approach” to take with anaplastic gliomas, but one could safely conclude that treatment decisions should not be based on MGMT promoter methylation.
For more information:
- DeAngelis LM. J Clin Oncol. 2009;doi:10.1200/JCO.2009.24.5985
- Wick W. J Clin Oncol. 2009;doi:10.1200/JCO.2009.23.6497.