Based on the phase III E3F05 trial, conducted by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN), the combination of radiation therapy and temozolomide appeared to be more effective than radiotherapy alone in the treatment of low-grade gliomas. The trial followed 172 patients for more than 10 years, and these results were presented as a late-breaking abstract at the 2024 Society of Neuro-Oncology Annual Meeting and published in Neuro-Oncology.1
David Schiff, MD
“We found that the 10-year survival rate was 70% with the combined treatment with temozolomide chemotherapy and radiation, compared to 47% with radiation alone as the initial approach. This discovery is important because until now, we have not had compelling evidence that temozolomide improves overall survival in grade 2 gliomas,” said lead investigator David Schiff, MD, the Harrison Distinguished Professor of Neurology, Neurological Surgery and Medicine and Co-Director of the UVA Neuro-Oncology Center at the University of Virginia.
Study Details and Key Findings
The E3F05 trial started in September 2009 and enrolled patients with low-grade gliomas who had not received prior radiation or chemotherapy. Trial participants were randomly assigned 1:1 to receive either radiation alone (50.4 Gy in 28 fractions) or radiation (50.4 Gy) with temozolomide followed by 12 4-week cycles of postradiation temozolomide. Accrual stopped 5 years later in 2014, after another cooperative group trial, RTOG 9802 (also funded by the National Cancer Institute) reported benefit from the addition of the chemotherapy regimen PCV (procarbazine, lomustine, and vincristine) to radiation in grade 2 gliomas.
“Because the RTOG 9802 trial was positive for a benefit from PCV chemotherapy, it was no longer ethical to have a radiation-alone arm in E3F05, which is why our trial was closed to accrual. Even though we could not enroll the entire group as planned, after following all patients on the trial, results reached statistical significance showing the benefit of combined-modality temozolomide vs radiation alone,” said Dr. Schiff.
Safety Profile
Although grade 3 or higher toxicity was more common in E3F05 trial participants treated with temozolomide compared with radiation alone, toxicity was consistent with prior studies of temozolomide. “There were no unexpected toxicities from the addition of temozolomide,” said Dr. Schiff. “We saw more fatigue, gastrointestinal distress (nausea), and myelosuppression (thrombocytopenia, neutropenia, etc.) but very similar to what has been reported many, many times.”
Dr. Schiff continued: “Importantly, the magnitude of survival benefit from the addition of temozolomide was similar in oligodendrogliomas and astrocytomas. This finding stands in contrast to some uncontrolled and retrospective studies suggesting that temozolomide may be significantly less effective against oligodendrogliomas than PCV.”
DISCLOSURE: For full disclosures of the study authors, visit academic.oup.com.
REFERENCE
1. Schiff D, O’Neill A, Brown P, et al: LTBK-07: Progression-free and overall survival results of ECOG-ACRIN E3F05: A phase 3 intergroup trial of radiation ± temozolomide for grade II gliomas. Neuro-Oncology 26(suppl 8):viii1-viii2, 2024.
