Top Line: First interim results of the CATNON trial demonstrated a big benefit with the addition of adjuvant temozolomide (TMZ) following radiation for non-codeleted anaplastic astrocytomas (AA).
The Study: This week finally brings us the second interim analysis and along with it some answers on the utility of TMZ concurrent to radiation. As a reminder, because this is a trial you’ll want to remember, this huge international effort randomized 751 patients with non-codel AA’s in a 2×2 design to radiation +/- concurrent and +/- 12 months of adjuvant TMZ. Because it was designed in 2007, MGMT and IDH status were not mandated. Only 31% had a gross total resection, 47% a subtotal and 20% biopsy only. At a median follow-up of over 4.5 years, there were finally enough survival events to decree that adding concurrent TMZ does not improve overall survival (OS) enough to meet statistical significance: 5.5 years with concurrent versus 5 years without. Receipt of adjuvant TMZ, on the other hand, continues to result in a significant advantage by any standard: 6 years 10 months with adjuvant versus 3 years 11 months without. Whoa. Another important conclusion was that IDH mutation status was strongly prognostic and predictive of treatment benefit. Roughly 60% had an IDH1 or IDH2 mutation, and their median OS was 8 years 2 months compared to just 1 year 8 months for IDH-wt tumors. Finally, the benefit of adjuvant TMZ was only seen in IDH-mutated patients with an increase in 5-year OS from 65 → 82% and an increase in median OS from 5 years 8 months → 9 years 6 months. In contrast, those with IDH-wt had no benefit from either concurrent or adjuvant TMZ.
TBL: “The benefit from temozolomide in anaplastic astrocytoma is derived from the adjuvant phase of the treatment and is observed only in patients with IDH1 or IDH2 mutant tumours.” | van den Brent, Lancet Oncol 2021