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Adjuvant Temozolomide Benefit Confirmed For 1p/19q Non-Co-Deleted Anaplastic Glioma

Updated CATNON results show overall survival advantage with adjuvant, but not concurrent, temozolomide with radiotherapy for IDH1/2-mutated, 1p/19q non-co-deleted anaplastic glioma
21 May 2021
Anticancer Agents;  Central Nervous System Malignancies;  Personalised/Precision Medicine

Author: By Lynda Williams, Senior medwireNews Reporter 

 

medwireNews: The second interim analysis of the CATNON study has shed further light on the use of temozolomide in adults undergoing radiotherapy for newly diagnosed 1p/19q non-co-deleted anaplastic glioma. 

The phase III trial investigators say the update confirms the initial report of a significant survival (OS) benefit with 12 cycles of adjuvant temozolomide 150–200 mg/m2 on days 1–5 of a 4-week cycle, with treatment beginning 4 weeks after completion of radiotherapy. 

After a median 55.7 months of follow-up, the median OS was 82.3 months with adjuvant temozolomide versus 46.9 months without the chemotherapy agent, giving a significant hazard ratio for death of 0.64.  

By contrast, concurrent temozolomide 75 mg/m2 every day during radiotherapy showed no such OS benefit over radiotherapy alone, with median durations of 66.9 months and 60.4 months, respectively, report Martin van den Bent, from the Erasmus MC Cancer Institute in Rotterdam, the Netherlands, and co-workers. 

But further analysis revealed that only participants with tumours positive for an IDH1 or IDH2 mutation derived a significant OS benefit with adjuvant temozolomide, whereas patients with tumours wild-type for these alterations had no benefit from the addition of the chemotherapy agent to radiotherapy. 

Moreover, the researchers report a “slight separation of the survival curves” after concurrent temozolomide in patients with IDH1 or IDH2 mutated tumours, and hypothesise that “with longer follow-up, an overall survival signal might emerge similar to observations in studies on low-grade glioma and on anaplastic oligodendroglioma.” 

The investigators also looked at the impact of MGMT promotor methylation status in patients with and without IDH1 or IDH2 mutations. While multivariable analysis suggested that MGMT status may be an independent predictor of positive outcome in IDH1 or IDH2 mutated tumours, there was no such correlation among IDH1 and IDH2 wild-type tumours. 

“Taken together, the CATNON trial shows that the benefit from temozolomide is derived from the adjuvant phase and is limited to patients with IDH1 or IDH2 mutant anaplastic astrocytoma”, Martin van den Bent and co-workers write in The Lancet Oncology

For this population, “the standard of care consists of 59.4 Gy radiotherapy in 33 fractions followed by 12 cycles of adjuvant temozolomide chemotherapy”, they conclude. 

Reference 

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 studyLancet Oncol; Advance online publication 14 May 2021. DOI: 10.1016/S1470-2045(21)00090-5 

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2021 Springer Healthcare part of the Springer Nature group

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