Eflornithine Plus Lomustine Demonstrates Significant Survival Benefit for Molecularly Defined Grade 3 IDH-Mutant Astrocytoma
Key Clinical Takeaways
- Design/Population: The phase 3 STELLAR trial was a randomized, open-label study evaluating eflornithine plus lomustine versus lomustine alone in 343 patients with recurrent anaplastic astrocytoma. Eligible patients were ≥18 years of age, had first recurrence ≥6 months after radiation, KPS ≥ 70, and no imaging consistent with grade 4 glioblastoma. Patients received eflornithine (2.8 g/m² TID, 2 of every 3 weeks) with lomustine (90 mg/m² every 6 weeks) or lomustine alone (110 mg/m² every 6 weeks). The primary end point was overall survival (OS).
- Key Outcomes: Molecular reclassification by 2021 WHO criteria identified 196 IDH-mutant, CDKN2A/B-intact grade 3 astrocytomas, 33 IDH-mutant, CDKN2A/B-loss grade 4 astrocytomas, and 106 IDH–wild-type grade 4 glioblastomas. In grade 3 IDH-mutant astrocytoma, eflornithine plus lomustine improved median OS (34.9 vs 23.5 months; HR, 0.64; P = .0136) and PFS (15.8 vs 7.2 months; HR, 0.57; P = .0113). BICR confirmed strong correlation between investigator- and centrally assessed PFS (P = .0305) and between OS and PFS (P = .0001).
- Clinical Relevance: The combination of eflornithine and lomustine provides meaningful and durable OS and PFS benefits in molecularly-defined grade 3 IDH-mutant astrocytoma. These results confirm and expand prior findings, supporting eflornithine plus lomustine as a potential new therapeutic standard for this patient population.
Updated molecular analyses from the phase 3 STELLAR trial demonstrated that the combination of eflornithine and lomustine significantly improved survival compared with lomustine alone among patients with molecularly-defined grade 3 IDH-mutant astrocytoma.
These findings were presented by Howard Colman, MD, PhD, of the Huntsman Cancer Institute, Salt Lake City, Utah, at the 2025 Society for Neuro-Oncology (SNO) Annual Meeting in Honolulu, Hawaii.
In this open-label, phase 3 trial, investigators enrolled 343 patients aged ≥ 18 years who had experienced first recurrence ≥6 months after radiation and had no imaging findings consistent with grade 4 glioblastoma. Patients were randomized to receive 90 mg/m² of lomustine every 6 weeks either alone or in combination with 2.8 g/m² of eflornithine 3 times daily once every 2 of 3 weeks. Updated molecular testing reclassified patients into 3 molecular subtypes based on the 2021 WHO criteria: 196 with IDH-mutant, CDKN2A/B-intact grade 3 astrocytoma, 33 with IDH-mutant, CDKN2A/B-loss grade 4 astrocytoma, and 106 with IDH–wild-type grade 4 glioblastoma. Primary end points included overall survival (OS) and progression-free survival (OS).
At analysis, among patients with grade 3 IDH-mutant astrocytoma, median OS was 34.9 months in the eflornithine plus lomustine arm and 23.5 months in the lomustine monotherapy arm (hazard ratio [HR], 0.64; P = .0136). Median PFS was 15.8 months and 7.2 months, respectively (HR, 0.57; P = .0113). Blinded independent central review (BICR) confirmed a strong correlation between investigator-assessed and centrally determined PFS (P = .0305) and between OS and PFS (P = .0001).
As Dr Colman concluded, “The clinically meaningful OS and PFS benefits observed with eflornithine in molecularly defined 2021 WHO CNS grade 3 astrocytomas are further confirmed and expanded based on additional molecular classification and blinded independent central review of PFS.”
Source:
Colman H, Lombardi G, Wong E, et al. Updated results of Phase 3 STELLAR trial: Eflornithine improves overall survival and blinded independent central review determined progression free survival in patients with recurrent WHO 2021 grade 3 IDH-mutant astrocytoma. Presented at the SNO Annual Meeting. November 19 - 23, 2025; Honolulu, Hawaii. Abstract CTNI-58.
