Adjuvant temozolomide, but not concurrent temozolomide, improved survival in patients with anaplastic glioma undergoing radiotherapy, according to research published in The Lancet Oncology.
All patients had anaplastic glioma without combined 1p/19q loss, but the survival benefit observed with adjuvant temozolomide was restricted to patients with IDH1- or IDH2-mutant tumors.
The patients were enrolled in the phase 3 CATNON trial (ClinicalTrials.gov Identifier: NCT00626990), which was designed to assess the addition of concurrent temozolomide, adjuvant temozolomide, or both current and adjuvant temozolomide to radiotherapy.
The study included 751 adults with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas. The patients were randomly assigned to 4 treatment arms: radiotherapy alone (n=189), radiotherapy with concurrent temozolomide (n=188), radiotherapy with adjuvant temozolomide (n=186), or radiotherapy with concurrent and adjuvant temozolomide (n=188).
The proportion of patients with IDH1/2 mutations was well balanced across the 4 groups. The primary endpoint was overall survival (OS) in the intention-to-treat population.
At a median follow-up of 55.7 months, the median OS was similar with and without concurrent temozolomide — 66.9 months and 60.4 months, respectively (hazard ratio [HR], 0.97; 99.1% CI, 0.73-1.28; P =.76).
The median OS was significantly longer with adjuvant temozolomide than without it — 82.3 months and 46.9 months, respectively (HR, 0.64; 95% CI, 0.52-0.79; P <.0001).
The median OS was significantly longer in patients with IDH1/2-mutant tumors than in those with wild-type IDH1/2 — 98.4 months and 19.9 months, respectively (HR, 0.14; 95% CI, 0.12-0.18; P <.0001).
Among patients with wild-type IDH1/2, there was no significant difference in OS with or without concurrent temozolomide (P =.82), and there was no significant difference in OS with or without adjuvant temozolomide (P = .98).
Among patients with mutant IDH1/2, there was no significant difference in median OS with and without concurrent temozolomide — 116.6 months and 91.8 months, respectively (HR, 0.80; 95% CI, 0.58-1.10; P =.17).
However, patients with IDH1/2-mutant tumors did have a significant difference in median OS with and without adjuvant temozolomide — 116.6 months and 77.8 months, respectively (HR, 0.48; 95% CI, 0.35-0.67; P <.0001).
Grade 3/4 hematologic toxicities occurred in 9% of patients in the concurrent temozolomide group and 15% of patients in both groups with adjuvant temozolomide. There were no treatment-related deaths reported during the study.
“[T]he present analysis shows that 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 tumors,” the researchers wrote.
Disclosures: This research was supported by Merck Sharpe & Dohme. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
van den Bent MJ, Tesileanu CMS, Wick W, et al. 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. 2021;22(6):813-823. doi:10.1016/S1470-2045(21)00090-5