STELLAR: Phase III, Randomized, Open-Label Study of Eflornithine Plus Lomustine Versus Lomustine Alone in Patients With Recurrent Grade 3 Astrocytoma
Mené sur 343 patients atteints d'un astrocytome de grade III récidivant, cet essai international de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'ajout d'éflornithine à la lomustine
Purpose: STELLAR (ClinicalTrials.gov identifier: NCT02796261) was a phase III, randomized, open-label trial of eflornithine + lomustine versus lomustine monotherapy in patients with recurrent grade 3 astrocytoma.
Methods: At trial initiation, eligibility criteria included: age ≥18 years, anaplastic astrocytoma (2016 WHO CNS Tumor classification [WHO CNS4]), first recurrence ≥6 months after radiation and temozolomide (TMZ), Karnofsky performance status ≥70, and no imaging findings consistent with grade 4 glioblastoma. Random assignment (1:1) was stratified by isocitrate dehydrogenase (IDH) mutation, age, resection extent, and geography. Patients received eflornithine (2.8 g/m2 orally, every 8 hours [2 weeks on, 1 week off]) + lomustine (90 mg/m2 orally, once every 6 weeks), or lomustine monotherapy (110 mg/m2 once every 6 weeks). The primary end point was overall survival (OS).
Results: Among 343 patients randomly assigned across 74 sites in eight countries, there was no difference in survival between eflornithine + lomustine and lomustine monotherapy (median OS 23.4 v 20.3 months, hazard ratio [HR], 0.94). Following changes in classification and grading in the 2021 WHO CNS5, a subset analysis of patients with IDH-mutant, grade 3 astrocytoma (n = 196), defined in 2024, before unblinding, showed clinically meaningful improvements in median OS with eflornithine + lomustine versus lomustine monotherapy (34.9 v 23.5 months, HR, 0.64) and median progression-free survival (PFS, 15.8 v 7.2 months, HR, 0.57). No differences were observed among patients with CNS grade 4 disease. Grade ≥3 treatment-emergent adverse events of relevance were related to reversible myelosuppression (eflornithine + lomustine 42% v lomustine monotherapy 29% of patients) and hearing impairment (24% v 0%). No new safety signals were identified.
Conclusion: Clinically meaningful improvements were observed; eflornithine + lomustine doubled PFS and improved OS in patients with recurrent IDH-mutant, grade 3 astrocytoma, but not grade 4 tumors, after prior radiotherapy and TMZ, consistent with its cytostatic mechanism of action.
Journal of Clinical Oncology , résumé, 2025