Targeted and systemic therapies for recurrent adult ependymomas: real-world outcomes from a single institution and concise literature review.

BACKGROUND

Recurrent adult ependymomas lack standard systemic therapies and evidence on chemotherapy and targeted agents is limited. This study aimed to retrospectively evaluated outcomes of systemic therapies, including targeted combinations, in a real-world cohort.

METHODS

Adult patients with intracranial or spinal ependymoma treated at our institution between 2013 and 2025 who received at least one systemic line at recurrence were included. Tumor response was assessed according to RANO criteria. Primary endpoints were disease control rate (DCR) and progression-free survival (PFS). Secondary endpoints were overall survival from the start of the first line treatment (OSt) and overall survival from diagnosis (OS).

RESULTS

Among 47 patients, 12 received systemic therapy at recurrence. The median follow up duration for the entire cohort was 28.3 months. Temozolomide (TMZ) was the most commonly used agent (n=12). TMZ monotherapy achieved a DCR of 57% with 6- and 12-month PFS rates of 85.7% and 57.1%, respectively. Targeted therapy was administered to 7 patients: the TMZ-Lapatinib combination provided limited benefit (DCR 33%, median PFS 2.9 months), bevacizumab-based regimens showed variable efficacy; bevacizumab alone achieved a DCR of 33% with one case of prolonged stabilization (>58 months), while bevacizumab plus fotemustine yielded a PFS of 14.1 months. Treatments were generally well tolerated, with limited grade 3 toxicities. Sequential systemic therapy, up to five lines, was feasible in selected cases. Median OSt was not reached; 12-month OS was 66.7%.

CONCLUSIONS

This real-world analysis indicates that temozolomide is feasible and associated with disease stabilization in selected patients, while bevacizumab-based combinations showed signals of clinical activity in recurrent adult ependymomas. Prospective, biomarker-driven multicenter trials are warranted to optimize systemic strategies in this rare disease.