First-line temozolomide did not offer improvements over radiotherapy for high-risk, low-grade glioma, according to a large, international, randomized trial. The two treatment strategies did not have a statistically significant difference for progression-free survival, although radiotherapy was numerically favored. However, molecular tumor characterization may allow the treatment approach to be personalized and the one or the other treatment modality to be selected.
This trial, conducted by the European Organisation for the Research and Treatment of Cancer, was presented orally June 1 at the 2013 Annual Meeting of the American Society of Clinical Oncology in Chicago, Illinois.
The trial randomized 477 patients from 18 countries after they were molecularly stratified for 1p status. The patients received either radiotherapy (240 patients) or chemotherapy with temozolomide (237 patients), which is a drug with activity in low-grade glioma. The trial’s results indicate that first-line treatment with temozolomide compared to radiotherapy does not improve progression-free survival in these high-risk, low-grade glioma patients.
“This is the first study in primary brain tumor to prospectively evaluate molecular markers. In the future, diagnosis of low-grade glioma will be substituted by a more differentiated molecular tumor characterization upon which treatment strategies will depend. The data are preliminary – as median overall survival has not yet been reached. Good wine needs aging,” said presenter Brigitta Baumert, MD, PhD, of the Radiation Oncology Department of Maastricht University.
This trial was designed for patients with a prognostic profile that indicated a poor outcome. Outcomes of low-grade glioma vary widely, and treatment can be deferred in patients without additional risk factors.
This study also sought to identify prognostic molecular factors that might assist in treatment decisions. When the study was conceived, the presence of a chromosomal deletion on the short arm of chromosome 1 was known to be prognostically important, and so patients were stratified before randomization. Other markers will be analyzed now that the study is complete, with the aim of clarifying why some patients have a much better disease evolution than others.
At a median follow-up of 45.5 months and after the tumors of 246 patients had progressed, there was no statistical difference in progression-free survival, the primary end point. Overall toxicity was mild. Grade three hematological toxicity was observed in 9% of the temozolomide-treated patients.
Secondary analyses included overall survival and the impact of 1p status. Median overall survival was not yet reached. The 1p deletion was confirmed to be a positive prognostic factor with either treatment.