Adjuvant Temozolomide in 1p/19q Non-Codeleted Anaplastic Glioma

Key Points

  • In patients with 1p/19q non-codeleted anaplastic glioma, adjuvant temozolomide was associated with significantly improved overall survival.
  • Five-year overall survival was 55.9% vs 44.1% for adjuvant temozolomide vs no adjuvant temozolomide.

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 van den Bent et al.

Study Details

In the open-label 2 x 2 factorial trial, 745 adult patients with newly diagnosed disease were randomized 1:1:1:1 between December 2007 and September 2015 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.

Overall Survival

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). When MGMT promoter methylation status that became known after randomization was included in the analysis, the hazard ratio was 0.65 (95% 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%.

Adverse Events

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. Grade 3 or 4 increases in aminotransferases occurred in 1% of patients receiving temozolomide.

The investigators concluded: “Adjuvant temozolomide chemotherapy was associated with a significant survival benefit in patients with newly diagnosed non-co-deleted anaplastic glioma. Further analysis of the role of concurrent temozolomide treatment and molecular factors is needed.”

They noted: “The standard of care for 1p/19q non-co-deleted anaplastic glioma should be surgery followed by radiotherapy and 12 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. Further follow-up will be necessary to understand whether temozolomide given concurrently with radiotherapy also improves survival.”

The study was funded by Schering Plough and MSD.

Martin J van den Bent, MD, of the Brain Tumour Centre at Erasmus MC Cancer Institute, Rotterdam, is the corresponding author of The Lancet article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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