A phase 3 clinical trial has established that the addition of temozolomide to radiation therapy significantly improves overall survival in patients with grade II gliomas. The ECOG-ACRIN E3F05 trial, a randomized study, provides compelling evidence supporting the use of temozolomide in this patient population, addressing a previous lack of definitive data. Led by David Schiff, MD, of UVA Cancer Center, the trial's findings are poised to influence treatment strategies for these slow-growing brain tumors.
The ECOG-ACRIN E3F05 trial enrolled 172 patients with grade II gliomas who had not previously received radiation or chemotherapy. Participants were randomized to receive either radiation therapy alone or radiation therapy in combination with temozolomide. The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), quality of life, and cognitive function.
Survival Benefits
After a median follow-up of 117 months, the trial demonstrated a significant improvement in overall survival for patients treated with the combination of temozolomide and radiation. The 10-year survival rate was 70% in the temozolomide arm compared to 47% in the radiation-alone arm (HR = 0.54; P = .03). This translates to a 53% reduction in the risk of death with the addition of temozolomide.
"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," said Dr. Schiff. "This discovery is important, because until now, we have not had compelling evidence that temozolomide improves overall survival in grade 2 gliomas."
Impact on Clinical Practice
The results of the ECOG-ACRIN E3F05 trial are expected to have an immediate impact on clinical practice. Temozolomide offers a more convenient and less toxic alternative to PCV (procarbazine, lomustine, and vincristine) chemotherapy, which has been used in the treatment of grade II gliomas based on previous trials. The new data provide strong support for the use of temozolomide as a standard treatment option.
"This provides reassurance to clinicians who would prefer their patients receive a better tolerated chemotherapy and simpler regimen," Dr. Schiff noted.
Additional Findings
While the trial demonstrated a significant improvement in overall survival, there was no statistically significant difference in progression-free survival between the two treatment arms (HR 0.76; 95% CI, 0.44-1.28; P = .30). The overall survival benefit was observed in patients both with and without 1p/19q codeletions, with hazard ratios of 0.56 and 0.53, respectively.
Grade 3 or higher toxicities, including thrombocytopenia (11%) and neutropenia (5%), were more frequent in patients treated with temozolomide.
Future Research
Dr. Schiff emphasized the importance of further research to refine the understanding of optimal treatment strategies for grade II gliomas. Ongoing analyses include the use of methylation profiling to classify tumors according to current molecular classifications and assess which patients are most likely to benefit from temozolomide. Additionally, researchers are evaluating the impact of temozolomide on quality of life and cognitive function.
"Although radiation has gotten much safer over time, there still is some potential long-term impact on quality of life and cognition in patients with glioma who receive radiation. We are tracking quality of life and cognitive function in the patients on this study. This will allow us to see if the addition of temozolomide has any impact — positive or negative — on functioning, and examine the course of quality of life and cognitive function over time prior to the tumor starting to grow again."
