As reported in the Journal of Clinical Oncology by Colman et al, the phase III STELLAR trial showed no difference in overall survival with the addition of eflornithine to lomustine in patients with recurrent grade 3 astrocytoma; however, marked progression-free survival and overall survival benefits with the combination were observed in the subgroup of patients with IDH-mutant disease.
Study Details
In the open-label trial, 343 patients from sites in eight countries were randomly assigned between 2016 and 2022 to receive eflornithine at 2.8 g/m2 orally every 8 hours for 2 weeks on/1 week off plus lomustine orally at 90 mg/m2 once every 6 weeks (n = 172), or lomustine monotherapy at 110 mg/m2 once every 6 weeks (n = 171). Patients had first recurrence at ≥ 6 months after radiation and temozolomide (TMZ), and no imaging findings consistent with grade 4 glioblastoma. The primary endpoint was overall survival.
Key Findings
Median follow-up was between 54 and 55 months in the two groups. Median overall survival was 23.4 months (95% confidence interval [CI] = 20.5–28.2 months) in the combination group vs 20.3 months (95% CI = 16.5–25.4 months) in the lomustine monotherapy group (hazard ratio [HR] = 0.95, 95% CI = 0.74–1.23, P = .703). No difference in progression-free survival was observed (8.9 vs 7.2 months, HR = 0.88, 95% CI = 0.65–1.20).
A subgroup analysis among 196 patients with IDH-mutant astrocytoma showed a median overall survival of 34.9 months (95% CI = 28.2–47.6 months) among 96 patients in the combination group vs 23.5 months (95% CI = 18.3–31.0 months) among 100 patients in the control group (HR = 0.64, 95% CI = 0.44–0.91). In this subgroup, median progression-free survival was 15.8 vs 7.2 months (HR = 0.57, 95% CI = 0.36–0.88). No significant differences in progression-free or overall survival were observed among patients with wild-type IDH.
Grade ≥ 3 adverse events included reversible myelosuppression (42% of the eflornithine plus lomustine group vs 29% of the lomustine monotherapy group) and hearing impairment (24% vs 0%). No new safety signals were identified.
The investigators concluded: “Clinically meaningful improvements were observed; eflornithine plus lomustine doubled [progression-free survival] and improved [overall survival] 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.”
Howard Colman, MD, PhD, of Huntsman Cancer Institute, Department of Neurosurgery, University of Utah, Salt Lake City, Utah, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Orbus Therapeutics Inc. For full disclosures of all study authors, visit ascopubs.org.
