A single-arm phase 2 study of abemaciclib in adult patients with recurrent grade 3 oligodendroglioma.

Abstract

Background: Novel treatments are needed for oligodendroglioma that has recurred following radiotherapy (RT) and chemotherapy. The cyclin D1-CDK4 axis is frequently dysregulated in oligodendroglioma. Abemaciclib is a selective CDK4/6 inhibitor that achieves pharmacologically relevant concentrations in brain tumor tissue.

Methods: We conducted a single-arm, phase 2 trial evaluating the efficacy of abemaciclib in patients with recurrent oligodendroglioma, isocitrate dehydrogenase (IDH)-mutant and 1p/19q-codeleted, WHO grade 3, following prior RT and ≥1 line of alkylating chemotherapy. Patients received abemaciclib 200 mg twice daily. The primary endpoint was progression-free survival at 6 months (PFS-6).

Results: Ten patients were enrolled. The most common treatment-related adverse event was grade 1-2 diarrhea, occurring in all patients. Five patients (50%) were alive and progression-free at 6 months, below the minimum required (80%) to meet the primary endpoint. In patients with enhancing tumor (n = 9), best response was partial response in 2 patients (objective radiographic response = 22.2%; duration of response [DOR] 13.1 and 7.7 months), stable disease (SD) in 3 patients (33.3%; duration of SD 17.0, 6.7, and 2.5 months), progressive disease in 3 patients (33.3%), and nonevaluable in 1 patient (11.1%). The patient with nonenhancing tumor showed SD lasting 10.2 months. Median PFS was 7.7 months (95% CI, 1.7-13.1 months); median overall survival was not reached (median follow-up 17 months).

Conclusions: The efficacy of abemaciclib in recurrent grade 3 oligodendroglioma was inadequate to warrant further evaluation as monotherapy in unselected patients. However, given the objective responses and durable disease control observed in a subset of patients, further studies are warranted to identify subgroups that may benefit.