Dr Colman on Outcomes With Eflornithine in Grade 3 Anaplastic Astrocytoma

“When the current grade 3 astrocytoma population—the IDH-mutant, CDKN2-intact population—was analyzed, there was a very clinically significant and statistically significant benefit in terms of OS and PFS [with eflornithine plus lomustine vs lomustine alone].”

Howard Colman, MD, PhD, Jan M. Huntsman Presidential Professor, Department of Neurosurgery, member, Brain Tumor Research Team, and leader, Center for Neurologic Cancers, Huntsman Cancer Institute, University of Utah, discusses findings from the phase 3 STELLAR trial (NCT02796261) investigating eflornithine plus lomustine vs lomustine alone in patients with recurrent, IDH-mutant, grade 3 anaplastic astrocytoma.

The intent-to-treat (ITT) population of the STELLAR study enrolled patients across 3 different subsets: IDH-mutant, CDKN2-intact tumors; IDH-mutant tumors with CDKN2 loss; and IDH wild-type tumors. Of note, the World Health Organization (WHO) definition of anaplastic astrocytoma evolved as the study was being conducted, leading trial investigators to evaluate findings in both the ITT population and among patients who fit the revised, molecularly defined WHO 2021 anaplastic astrocytoma diagnostic criteria.

The final analysis of the ITT population showed slight numerical improvements in progression-free survival (PFS) and overall survival (OS) among patients who received eflornithine (n = 172) vs lomustine alone (n = 171); however, these findings were not statistically significant, Colman says. The median OS was 23.4 months in the eflornithine arm vs 20.3 months in the comparator arm (HR, 0.94).

Notably, data from a prespecified subset analysis showed statistically significant and clinically meaningful PFS and OS benefits with eflornithine vs lomustine alone in the subgroup of patients with IDH-mutant, 2021 WHO–defined grade 3 astrocytoma (n = 194). In this population, the median OS was 34.9 months with eflornithine vs 23.5 months with lomustine alone (HR, 0.64; log-rank P = .016). The median PFS in these respective arms was 15.8 months and 7.2 months (HR, 0.58; log-rank P = .015).