Multinational phase 3 trial of lomustine with or without eflornithine in patients with recurrent grade 3 astrocytoma

The phase 3 STELLAR trial, at 74 centers in eight countries, evaluated addition of eflornitine to lomustine among patients with recurrent grade 3 astrocytoma. Adult patients with first recurrence ≥ 6 months after radiation and temozolomide and Karnofsky performance status ≥ 70 were randomized 1:1 to eflornithine plus lomustine (n=169) or lomustine alone (n=150). Randomization was stratified by IDH mutation, age, resection extent, and geography. The primary endpoint was overall survival. Addition of eflornithine to lomustine did not improve OS in the overall population (median 23.4 versus 20.3 months), but was associated with improved OS in the subset of patients with IDH-mutation (n=196; median 34.9 versus 23.5 months; HR 0.64). In this subset, also the median progression-free survival was improved with addition of eflornithine (15.8 versus 7.2 months; HR 0.57). Grade ≥ 3 treatment-related adverse events were related to reversible myelosuppression (42% versus 29%) and hearing impairment (24% versus 0%). The authors conclude that addition of eflornithine to lomustine was associated with survival improvements among patients with recurrent IDH-mutant grade 3 astrocytoma