Neuro-Oncology · Radiation / Medical Oncology · 10 September 2026

CATNON

In newly diagnosed 1p/19q non-codeleted grade 3 astrocytoma, does temozolomide given after radiotherapy improve survival, and does concurrent temozolomide add benefit?

Population

751 adults with newly diagnosed 1p/19q non-codeleted grade 3 glioma; final molecular analysis identified 444 IDH-mutant tumours

Intervention

Radiotherapy followed by 12 cycles of adjuvant temozolomide, with or without concurrent TMZ

Comparator

Radiotherapy without adjuvant temozolomide

Primary endpoint

Overall survival

Absolute Effect

Overall survival · IDH-mutant

12.5 years median OS

Adjuvant TMZ after RT · final median follow-up 10.9 years

NNT: Not quantifiable for the primary endpoint. The most clinically informative absolute measure is the substantial median-survival difference.

Concurrent TMZ

No demonstrated OS benefit

IDH-mutant HR 0.81 (95% CI 0.63–1.04; P=.09)

Interpretation: the survival signal is driven by the adjuvant phase, not by adding concurrent TMZ.

The big takeaway

Adjuvant temozolomide is the critical component. In IDH-mutant, 1p/19q non-codeleted grade 3 astrocytoma, radiotherapy followed by 12 cycles of adjuvant TMZ substantially prolongs survival. The final CATNON analysis did not demonstrate an additional overall-survival benefit from concurrent TMZ during radiotherapy.

In the final analysis, after a median follow-up of 10.9 years and 499 observed events, adjuvant TMZ improved OS in IDH-mutant tumours with HR 0.54 (95% CI 0.42–0.69; P<0.0001). Median OS in patients with IDH-mutant tumours receiving adjuvant TMZ was 12.5 years. By contrast, concurrent TMZ did not significantly improve OS in the IDH-mutant subgroup (HR 0.81, 95% CI 0.63–1.04; P=.09).

The practical treatment sequence established by CATNON is therefore radiotherapy followed by 12 cycles of adjuvant temozolomide, rather than assuming that the Stupp-style concurrent-plus-adjuvant approach automatically adds benefit in this disease.

Absolute Effect interpretation

NNT: not quantifiable for the primary endpoint (overall survival). CATNON is a time-to-event trial and its mature headline result is most naturally expressed through the hazard ratio and median survival rather than a manufactured NNT. A median-survival difference should not be converted into an NNT.

This is an important Absolute Effect principle: NNT not being quantifiable does not mean the treatment lacks a large absolute effect. Here, the clinically meaningful finding is the long-term survival prolongation with adjuvant TMZ in IDH-mutant tumours.

NNH: not quantifiable. No single fixed-time toxicity endpoint provides a sufficiently central and robust basis for a trial-level NNH. Treatment-related toxicity and treatment burden should be reported directly.

Critical review

CATNON is especially important because it separates two commonly conflated concepts: temozolomide given concurrently with radiotherapy and temozolomide given after radiotherapy. The final molecular analysis shows that the clinically important survival effect is concentrated in the adjuvant phase and in IDH-mutant tumours.

The result also illustrates why treatment intensity should not be inferred from another tumour type. The absence of a demonstrated concurrent-TMZ OS benefit means that adding more chemotherapy around radiotherapy is not automatically better. The trial supports a specific sequence: definitive radiotherapy followed by prolonged adjuvant TMZ.

Primary sources

EORTC 26053-22033 CATNON final clinical and molecular analysis. Neuro-Oncology. Final analysis after median follow-up 10.9 years.

ASCO-SNO guideline rapid recommendation update: people with IDH-mutant, 1p/19q non-codeleted CNS WHO grade 3 astrocytoma should be offered radiotherapy with adjuvant temozolomide.

CATNON conclusion: Closure on concurrent chemotherapy in IDH mutant grade 3 astrocytoma. Neuro-Oncology. 2026.