Clinical trialPhase 3Brain tumours

Adjuvant and concurrent temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053-22054): second interim analysis of a randomised, open-label, phase 3 study

Lancet Oncol · 2021751 patients

van den Bent MJ, Tesileanu CMS, Wick W, et al. Lancet Oncol. 2021. 22:813-823

A newer report of this study has been published: Concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053-22054): final and exploratory analyses of a randomised, open-label, phase 3 trial (2026)

Study type: Clinical trial
Study name: CATNON (EORTC 26053-22054)
Phase: Phase 3
Design: Open-label randomised 2×2 factorial trial (four groups, 1:1:1:1), 137 centres in Australia, Europe and North America
Sample size: 751 patients
Source: Lancet Oncol · 2021
Trial registration: NCT00626990

In plain words

This study looked at people with a grade 3 glioma (without the 1p/19q genetic change that marks oligodendroglioma) to find the best time to take temozolomide tablets. It found that taking temozolomide after radiotherapy had finished (12 cycles) clearly helped people live longer, but taking it at the same time as radiotherapy gave no extra benefit. The benefit was mainly in patients whose tumour had an IDH mutation, so molecular testing of the tumour is very important for treatment decisions.

Key results

82.3 vs 46.9 months

Adjuvant temozolomide: median overall survival

HR 0.64 (95% CI 0.52–0.79); p<0.0001

66.9 vs 60.4 months

Concurrent temozolomide: median overall survival

HR 0.97 (99.1% CI 0.73–1.28); p=0.76; futility declared

Median overall survival 114.4 vs 68.2 months

IDH-mutant tumours: any temozolomide vs radiotherapy alone

HR 0.53 (95% CI 0.38–0.74) (full paper). In IDH-wildtype tumours, neither concurrent nor adjuvant temozolomide improved survival

Drugs in this study:Temozolomide (Temodal)

Dose and schedule cards

Radiotherapy followed by 12 cycles of adjuvant temozolomide (CATNON)

IDH-mutant astrocytoma (anaplastic glioma without 1p/19q codeletion), grade 3, and grade 2 when adjuvant chemotherapy is given; WHO PS 0 to 2Cycle length: Every 28 daysOn the page “Brain tumours” · IDH-mutant gliomas (astrocytoma and oligodendroglioma)

IDH-mutant astrocytoma (anaplastic glioma without 1p/19q codeletion), grade 3, and grade 2 when adjuvant chemotherapy is given; WHO PS 0 to 2

Drug	Dose	Route	Schedule
Radiotherapy
Radiotherapy	59.4 Gy in 33 fractions	External beam radiotherapy	Daily
Adjuvant: starting 4 weeks after the end of radiotherapy
Temozolomide (cycle 1)	150 mg/m² once daily	Oral	Days 1 to 5
Temozolomide (cycles 2 to 12)	200 mg/m² if there was no or minimal toxicity in cycle 1	Oral	Days 1 to 5

Cycle length: Every 28 days
Duration: 12 cycles (about 1 year)

Temozolomide concurrent with radiotherapy (75 mg/m² daily) gave no significant benefit; the benefit came from adjuvant temozolomide. Blood count monitoring, dose reduction and liver tests for temozolomide as in the temozolomide “Common safety considerations” in the glioblastoma regimens. Dose source:.

On the page “Brain tumours” · IDH-mutant gliomas (astrocytoma and oligodendroglioma)

Newly diagnosed anaplastic astrocytoma (adjuvant)

After radiotherapyOn the page “Temozolomide (Temodal)” · Dose and schedule (FDA label and key trials)

After radiotherapy

Drug	Dose	Route	Schedule
Cycle 1
Temozolomide	150 mg/m² a day	Oral	Days 1 to 5
Cycles 2 to 12
Temozolomide	200 mg/m² a day (if there was no or minimal toxicity in cycle 1)	Oral	Days 1 to 5

Cycle length: Every 28 days, starting 4 weeks after the end of radiotherapy
Duration: 12 cycles

As in the FDA label; in the CATNON trial (anaplastic glioma without 1p/19q co-deletion), 12 four-weekly cycles of 150 to 200 mg/m² on days 1 to 5 were also given after radiotherapy of 59.4 Gy in 33 fractions.

On the page “Temozolomide (Temodal)” · Dose and schedule (FDA label and key trials)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Radiotherapy alone

Focal radiotherapy (3D conformal or IMRT) 59.4 Gy in 33 fractions.

2Radiotherapy + concurrent temozolomide

Radiotherapy 59.4 Gy in 33 fractions with oral temozolomide 75 mg/m² daily throughout radiotherapy.

Monitoring: weekly blood counts during concurrent temozolomide; every 4 weeks during radiotherapy and adjuvant temozolomide, blood counts, liver and kidney tests and electrolytes.

3Radiotherapy + adjuvant temozolomide

Radiotherapy 59.4 Gy in 33 fractions; then, 4 weeks after the end of radiotherapy, 12 cycles of oral temozolomide on days 1 to 5 every 28 days: cycle 1 at 150 mg/m² per day and, if there was no or minimal toxicity, later cycles at 200 mg/m² per day.

Monitoring: weekly blood counts during concurrent temozolomide; every 4 weeks during radiotherapy and adjuvant temozolomide, blood counts, liver and kidney tests and electrolytes.

4Radiotherapy + concurrent and adjuvant temozolomide

Radiotherapy 59.4 Gy in 33 fractions with concurrent temozolomide 75 mg/m² daily, then, 4 weeks after the end of radiotherapy, 12 cycles of temozolomide (days 1 to 5 every 28 days; cycle 1: 150, then 200 mg/m² per day if tolerated).

Monitoring: weekly blood counts during concurrent temozolomide; every 4 weeks during radiotherapy and adjuvant temozolomide, blood counts, liver and kidney tests and electrolytes.

Source of the regimen details: Abstract and the "Treatment" section of the full paper (Lancet Oncol 2021, PMC8191233): radiotherapy 59.4 Gy in 33 fractions, concurrent temozolomide 75 mg/m² daily, adjuvant from 4 weeks after radiotherapy at 150 then 200 mg/m² on days 1 to 5 every 28 days for 12 cycles; IDH subgroup results from the full paper.

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Adults aged 18 years or older with newly diagnosed anaplastic (grade 3) glioma without 1p/19q co-deletion and WHO performance status 0 to 2. Stratified by centre, performance status, age, 1p loss of heterozygosity, presence of oligodendroglial elements and MGMT promoter methylation.

Endpoints

Primary endpoint: overall survival adjusted for stratification factors in the intention-to-treat population. The second interim analysis (after two-thirds of events had occurred) was designed to test superiority or futility of concurrent temozolomide.

Safety and side effects

The most common grade 3 and 4 toxicities were haematological: none in the radiotherapy-alone group, 16 of 185 (9%) in the concurrent temozolomide group and 55 of 368 (15%) in the two groups receiving adjuvant temozolomide. No treatment-related deaths were reported.

Clinical significance and place in guidelines

Based on CATNON, the EANO 2021 guideline considers radiotherapy followed by maintenance temozolomide the standard of care for IDH-mutant grade 3 astrocytoma (C: II; L: B). This study also showed that IDH-wildtype tumours (now often classified as glioblastoma) derived no clear benefit from temozolomide in this setting.

Limitations

Second interim analysis (data not fully mature); open-label design. The role of concurrent temozolomide in the IDH-mutant subgroup has not yet been definitively ruled out, and the final analysis is awaited. Subgroup analyses by IDH status were exploratory. Patients were classified before WHO 2021.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.