Background
CATNON/EORTC 26053-22054 was a 2×2 factorial phase III trial in newly diagnosed 1p/19q non-codeleted anaplastic glioma (grade 3), evaluating the independent contributions of concurrent temozolomide (during RT) and adjuvant temozolomide (after RT) to overall survival.
Interventions and follow up
Arm A: Radiotherapy alone (59.4 Gy)
Arm B: RT + concurrent TMZ (75mg/m²/day)
Arm C: RT → adjuvant TMZ (12 cycles, 150–200mg/m² days 1–5 q28d)
Arm D: RT + concurrent TMZ → adjuvant TMZ
Primary endpoint: overall survival
mFollow-up: 55.7mo (second interim analysis)
Arm B: RT + concurrent TMZ (75mg/m²/day)
Arm C: RT → adjuvant TMZ (12 cycles, 150–200mg/m² days 1–5 q28d)
Arm D: RT + concurrent TMZ → adjuvant TMZ
Primary endpoint: overall survival
mFollow-up: 55.7mo (second interim analysis)
Results
n: 751
Concurrent TMZ (mOS): 66.9 vs 60.4mo (HR 0.97, 99.1% CI 0.73–1.28, P=.76; futility) — no benefit
Adjuvant TMZ (mOS): 82.3 vs 46.9mo (HR 0.64, 95% CI 0.52–0.79, P<.0001)
By IDH status: adjuvant TMZ benefit confined to IDH-mutant; IDH-wildtype derived no benefit
Concurrent TMZ (mOS): 66.9 vs 60.4mo (HR 0.97, 99.1% CI 0.73–1.28, P=.76; futility) — no benefit
Adjuvant TMZ (mOS): 82.3 vs 46.9mo (HR 0.64, 95% CI 0.52–0.79, P<.0001)
By IDH status: adjuvant TMZ benefit confined to IDH-mutant; IDH-wildtype derived no benefit
Adverse events
Hematologic (grade 3–4): 15% with adjuvant TMZ vs 0% (RT alone); ~9% with concurrent TMZ — thrombocytopenia, neutropenia, lymphopenia
Nonhematologic: nausea, fatigue, constipation; AE-related discontinuation uncommon and no treatment-related deaths.
Nonhematologic: nausea, fatigue, constipation; AE-related discontinuation uncommon and no treatment-related deaths.
Conclusions
Adjuvant temozolomide, but not concurrent temozolomide, improved OS in 1p/19q non-codeleted anaplastic glioma. Benefit was IDH-mutation dependent, establishing molecular profiling as essential to treatment decisions in this tumor type.
Key Limitations
IDH status was a retrospective subgroup, not a stratification factor; the IDH-wildtype subset (now reclassified as glioblastoma under WHO 2021) dilutes the overall population. Concurrent-TMZ futility leaves its role unresolved in molecularly defined subsets. Long accrual spanned evolving diagnostic criteria.
Clinical Context
CATNON supports RT followed by 12 cycles of adjuvant temozolomide for IDH-mutant grade 3 (1p/19q non-codeleted) astrocytoma, reflected in ESMO and ASCO/SNO guidance. It reinforced molecular classification (IDH, 1p/19q) as central to glioma management and complements CODEL/PCV data in codeleted disease.