TY - JOUR
T1 - STELLAR
T2 - Phase III, Randomized, Open-Label Study of Eflornithine Plus Lomustine Versus Lomustine Alone in Patients With Recurrent Grade 3 Astrocytoma
AU - Colman, Howard
AU - Lombardi, Giuseppe
AU - Wong, Eric T.
AU - Walbert, Tobias
AU - Eoli, Marica
AU - Lassman, Andrew B.
AU - Peereboom, David M.
AU - Kizilbash, Sani H.
AU - Kamiya-Matsuoka, Carlos
AU - Pitz, Marshall W.
AU - Strowd, Roy E.
AU - Desjardins, Annick
AU - Kumthekar, Priya
AU - Mason, Warren
AU - Pellerino, Alessia
AU - Soffietti, Riccardo
AU - Butowski, Nicholas
AU - Forsyth, Peter A.
AU - Hamza, Mohamed A.
AU - Hau, Peter
AU - Lallana, Enrico
AU - Nabors, Burt
AU - Piccioni, David
AU - Uhlmann, Erik J.
AU - Welsh, Liam C.
AU - Wen, Patrick Y.
AU - Dietrich, Jorg
AU - Wang, Chao
AU - Levin, Victor A.
N1 - Publisher Copyright:
© 2025 American Society of Clinical Oncology
PY - 2026/3/10
Y1 - 2026/3/10
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105032203473
UR - https://www.scopus.com/pages/publications/105032203473#tab=citedBy
U2 - 10.1200/JCO-25-01204
DO - 10.1200/JCO-25-01204
M3 - Article
C2 - 41325560
AN - SCOPUS:105032203473
SN - 0732-183X
VL - 44
SP - 641
EP - 652
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 8
ER -