Both radiation and temozolomide may have meaningful single-modality antitumor activity against slow-growing, low-grade gliomas, according to recent findings presented by Schiff et al at the 2024 Society for Neuro-Oncology Annual Meeting (Abstract LTBK-07) and simultaneously published in Neuro-Oncology.
Study Methods and Results
In the phase III E3F05 trial (ClinicalTrials.gov identifier NCT00978458), researchers examined whether combined therapy using temozolomide and radiation therapy may be more effective compared with radiation therapy alone in 172 patients with slow-growing, low-grade gliomas. The median age of the 172 participants was 44 years (range = 19–78 years), 54% of whom were male. The trial participants were randomly assigned 1:1 to receive either radiation alone (50.4 Gy in 28 fractions) or radiation (50.4 Gy) in combination with temozolomide followed by 12 4-week cycles of postradiation temozolomide.
The trial began in September 2009 and enrolled patients with low-grade gliomas who had not received prior radiation or chemotherapy. Accrual stopped 5 years later in 2014 after another cooperative group trial, RTOG 9802 reported benefit from the addition of procarbazine, lomustine, and vincristine (PCV) chemotherapy to radiation in patients with 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,” highlighted lead study author David Schiff, MD, the Harrison Distinguished Professor of Neurology, Neurological Surgery, and Medicine as well as Co-Director of the UVA Neuro-Oncology Center at the University of Virginia. “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,” he detailed.
Although grade 3 or higher toxicity was more common in the patients treated with temozolomide compared with radiation during the E3F05 trial, toxicity was consistent with prior studies of temozolomide. “There were no unexpected toxicities from the addition of temozolomide,” Dr. Schiff reported. “We saw more fatigue, gastrointestinal distress (nausea), and myelosuppression (thrombocytopenia [and] neutropenia) but very similar to what has been reported many, many times,” he added.
Conclusions
The results of the study may have an immediate clinical impact by demonstrating that temozolomide improves long-term survival in this patient population. “Since the results of RTOG 9802 came out in 2014, patients with grade 2 glioma are routinely receiving radiation plus chemotherapy. Some are getting PCV because that is what RTOG showed was beneficial. Others are getting radiation plus temozolomide because temozolomide is a lot easier for the oncologist to give and a lot less toxic for patients to take—and it doesn’t involve an intravenous infusion of vincristine. [However], until now, there really was no supporting evidence in grade 2 gliomas that temozolomide was beneficial,” Dr. Schiff indicated.
Pending correlative studies are investigating the quality-of-life and neurocognitive data collected from patients on both arms of the study as well as additional molecular analyses.
“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,” Dr. Schiff underscored.
Disclosure: The research in this study was funded by the National Institutes of Health’s National Cancer Institute through its National Clinical Trials Network. For full disclosures of the study authors, visit academic.oup.com.
