Neuro-OncologyLTBK-07. Progression-free and Overall Survival Results of ECOG-ACRIN E3F05: A Phase 3 Intergroup Trial of Radiation ± Temozolomide for Grade II Gliomas

A Phase 3 trial comparing radiation alone versus radiation with temozolomide for grade II gliomas provides new evidence for combination therapy approaches. The ECOG-ACRIN E3F05 study evaluated outcomes in 172 patients over a median follow-up period of 117 months, offering substantial data on survival benefits and toxicity profiles.

Study Design:

• Randomized 1:1 trial of radiation (50.4 Gy in 28 fractions) alone vs. radiation with concurrent and adjuvant temozolomide
• Inclusion criteria: Grade II gliomas, no prior radiation/chemotherapy, and either age >40, uncontrolled symptoms/seizures, or progression after observation
• 172 participants enrolled (median age 44, range 19-78, 54% male)
• 44% of participants had 1p/19q codeletion
• Stratification factors: 1p/19q codeletion status, age, KPS, pre-operative tumor diameter, contrast enhancement
• Study terminated early (January 2014) after RTOG 9802 showed PCV chemotherapy benefit

Key Findings:

• Overall survival superior in combination arm (HR 0.54, 95% CI 0.31-0.95, p=0.03)
• Five-year OS: 78% combination vs. 70% radiation alone
• Ten-year OS: 70% combination vs. 47% radiation alone
• Similar benefit in codeleted (HR 0.56) and non-codeleted tumors (HR 0.53)
• No significant difference in progression-free survival (HR 0.76, 95% CI 0.44-1.28, p=0.30)
• Grade 3+ toxicities in TMZ arm: thrombocytopenia (11%), neutropenia (5%)

HCN Medical Memo
The study provides robust evidence supporting combination therapy with temozolomide and radiation for grade II gliomas, regardless of 1p/19q codeletion status. Although managing additional toxicities requires careful monitoring, the substantial improvement in 10-year overall survival warrants strong consideration of this approach for eligible patients.

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