2nd Transatlantic EORTC/US cooperative group trial since implementation of European CTD: an EORTC led study

This past July, the EORTC 26053-22054 trial, the CATNON Intergroup trial, was activated in North America by the RTOG (Radiation Therapy Oncology Group). This trial follows an already successfully conducted trial led by the RTOG (Radiation Therapy Oncology Group) but is first large trans-Atlantic trial sponsored by the EORTC in the post European Clinical Trials Directive (CTD) era. The EORTC is the lead group for this study, and the RTOG is acting as the lead group for this study in North America.

The CATNON Intergroup trial is a randomized phase III trial investigating the optimal treatment for patients with newly diagnosed non-codeleted 1p/19q anaplastic glioma. It was previously shown in the EORTC 26981-22981/NCI-C CE3 trial that combined radiotherapy and temozolomide chemotherapy provides a superior outcome for patients with newly diagnosed glioblastoma compared to adjuvant treatment with radiotherapy alone. However, other studies have suggested that the benefit of this treatment might be limited to patients with tumors having a methylated (i.e., quiescent) MGMT gene promoter, and genetic analyses have shown a clear different outcome in anaplastic oligodendroglioma with co-deleted 1p/19q. It is now known that tumors with co-deleted 1p/19q are very sensitive to chemotherapy; virtually all tumors of this type respond to procarbazine, lomustine, and vincristine chemotherapy.

A rational conclusion, then, is that treatment of anaplastic gliomas needs to take into account both the histology as well as the genotype of the tumor. Still, the question remains as to how these results could be translated into appropriate therapeutic options and clinical benefit for patients with non-codeleted 1p/19q anaplastic glioma, and so the CATNON study is designed to establish whether concurrent or adjuvant temozolomide will improve the outcome of patients with non-codeleted 1p/19q anaplastic gliomas and will prospectively assess the prognostic and/or predictive value of MGMT methylation in this population.

The CATNON trial currently has 187 patients registered, 103 patients randomized, 35 EORTC sites activated, and one RTOG site activated. Recruitment will continue until 748 patients are randomized.

John Bean