Longitudinal PET RANO 1.0 and RANO 2.0 response assessment in vorasidenib-treated IDH-mutant gliomas: the VORAFET study

Conventional MRI may not fully reflect the biological activity of vorasidenib. PET may detect treatment-related metabolic changes before structural changes become evident on MRI. We evaluated longitudinal PET and MRI changes in patients with IDH-mutant gliomas receiving vorasidenib.

VORAFET is a longitudinal study of adults with IDH-mutant gliomas treated with vorasidenib. Eligible patients had predominantly non-enhancing WHO grade 2 or 3 gliomas, had not received prior radiotherapy or chemotherapy. The primary endpoint was longitudinal metabolic and structural imaging response according to PET RANO 1.0 and RANO 2.0. Integrated [¹⁸F]FET PET/MRI was performed at baseline and every 3 months.

Thirty-nine patients were included; at baseline, 23 and 29 had PET and MRI-measurable disease. As best response, PET RANO 1.0 identified 2 complete and 12 partial responses, yielding an ORR of 60.9%; median time to first response was 4.5 months (range 3-12 months). RANO 2.0 showed no complete or partial responses, whereas 5 patients achieved minor response at a median of 9 months (range 6-12 months). Progressive disease occurred in 6 of 39 patients (15.4%) according to PET RANO 1.0 and in 1 of 39 (2.6%) according to RANO 2.0. Patients with PET-PD more often had subtle contrast enhancement and showed higher baseline FLAIR volume, MTV, TBRmax, and TBRmean.

PET RANO 1.0 identified metabolic changes during vorasidenib treatment that were not always reflected by RANO 2.0 assessment. Longer follow-up is needed to clarify the relationship between PET metabolic changes and MRI findings and to determine their clinical significance.