Top Line: What is the benefit of concurrent and adjuvant temozolomide for high grade astrocytoma?
The Study: Anaplastic (Grade 3) astrocytomas (AA) are now recognized as distinct entities based on their IDH status with different underlying biology and different clinical behavior. IDH-mut AAs have better prognosis than their IDH-wt counterparts, which behave more like GBMs. Before this was all clear, though, the CATNON trial was designed to determine the role of TMZ in the management of AAs. The trial included 751 patients with AA, of whom 59% had IDH-mut tumors. After maximal safe resection, they were randomized in a 2×2 fashion to receive adjuvant radiation +/- concurrent TMZ followed by +/- 12 months of adjuvant TMZ. In the overall population, adjuvant TMZ significantly improved overall survival (HR 0.65, 0.54-0.77), but concurrent TMZ did not. The benefit was driven by those with IDH-mut tumors whose median OS was improved from 6→ 12.5 years with adjuvant TMZ. Though there was numeric improvement in median OS with concurrent TMZ (7.2→ 9.7 years), it did not reach statistical significance. In the IDH-wt subset, there was no improvement in survival with either concurrent or adjuvant TMZ. The paradox, though, is that because IDH-wt AAs are now considered similar to GBMs, they are typically treated with GBM protocols that include TMZ.
TBL: Final results from the CATNON trial demonstrate a significant improvement in survival with 12 months of adjuvant TMZ following surgery and adjuvant RT for grade 3, IDH-mut astrocytoma. Concurrent TMZ did not significantly influence OS outcomes, and the subset with IDH-wt tumors saw no improvements with TMZ. | van den Bent, Lancet Oncol 2025
The Study: Anaplastic (Grade 3) astrocytomas (AA) are now recognized as distinct entities based on their IDH status with different underlying biology and different clinical behavior. IDH-mut AAs have better prognosis than their IDH-wt counterparts, which behave more like GBMs. Before this was all clear, though, the CATNON trial was designed to determine the role of TMZ in the management of AAs. The trial included 751 patients with AA, of whom 59% had IDH-mut tumors. After maximal safe resection, they were randomized in a 2×2 fashion to receive adjuvant radiation +/- concurrent TMZ followed by +/- 12 months of adjuvant TMZ. In the overall population, adjuvant TMZ significantly improved overall survival (HR 0.65, 0.54-0.77), but concurrent TMZ did not. The benefit was driven by those with IDH-mut tumors whose median OS was improved from 6→ 12.5 years with adjuvant TMZ. Though there was numeric improvement in median OS with concurrent TMZ (7.2→ 9.7 years), it did not reach statistical significance. In the IDH-wt subset, there was no improvement in survival with either concurrent or adjuvant TMZ. The paradox, though, is that because IDH-wt AAs are now considered similar to GBMs, they are typically treated with GBM protocols that include TMZ.
TBL: Final results from the CATNON trial demonstrate a significant improvement in survival with 12 months of adjuvant TMZ following surgery and adjuvant RT for grade 3, IDH-mut astrocytoma. Concurrent TMZ did not significantly influence OS outcomes, and the subset with IDH-wt tumors saw no improvements with TMZ. | van den Bent, Lancet Oncol 2025