Martin J. van den Bent, MD
Interim results of the phase III CATNON trial (EORTC study 26053-22054) indicate a survival benefit of adjuvant temozolomide in 1p/19q non-codeleted anaplastic glioma. These findings were reported in The Lancet by Martin J. van den Bent, MD, of the Brain Tumour Centre at Erasmus MC Cancer Institute, Rotterdam, and colleagues.
In the open-label 2 × 2 factorial trial, 745 adult patients with newly diagnosed disease were randomized 1:1:1:1 to receive radiotherapy (59.4 Gy in 33 fractions of 1.8 Gy) alone (n = 187) or with (n = 185) adjuvant temozolomide (12 4-week cycles of 150–200 mg/m2 given on days 1–5) or to receive radiotherapy with concurrent temozolomide at 75 mg/m2/d with (n = 188) or without (n = 185) adjuvant temozolomide.
The primary endpoint was overall survival adjusted for performance status score, age, 1p loss of heterozygosity, presence of oligodendroglial elements, and MGMT promoter methylation status analyzed in the intention-to-treat population.
Survival and Safety
A planned interim analysis was performed after 219 deaths (41% of planned events) had occurred; at interim analysis, 745 of the planned 748 patients (99%) had been enrolled, and median follow-up was 27 months.
Median overall survival was not reached among patients receiving adjuvant temozolomide vs 41.1 months in the group that did not. The hazard ratio for overall survival adjusted for stratification factors was 0.65 (99.145% confidence interval [CI] = 0.45–0.93). Overall survival at 5 years was 55.9% vs 44.1%. Median progression-free survival was 42.8 vs 19.0 months (hazard ratio = 0.62, 95% CI = 0.50–0.76, on univariate analysis), and 5-year progression-free survival was 43.1% vs 24.3%.
Grade 3 or 4 adverse events occurred in 8% to 12% of the 549 patients who received temozolomide in any treatment group; they were primarily reversible hematologic adverse events, with the most common being thrombocytopenia (7%–9%). Except for constitutional and gastrointestinal events, most other nonhematologic adverse events were not judged to be related to treatment.
The investigators concluded: “Adjuvant temozolomide chemotherapy was associated with a significant survival benefit in patients with newly diagnosed non-codeleted anaplastic glioma.”
They noted: “The standard of care for 1p/19q non-codeleted anaplastic glioma should be surgery followed by radiotherapy and twelve 4-week cycles of temozolomide given on days 1–5. Ongoing molecular research within this trial will show whether IDH1 and IDH2 mutational status and MGMT promoter methylation can be used to identify the patients who will benefit most from temozolomide chemotherapy.” ■