FGFR Inhibitors for Treatment of Primary CNS Tumors

BACKGROUND

Dysregulation of fibroblast growth factor receptor (FGFR) signaling has been observed in central nervous system (CNS) tumors, with FGFR inhibitors associated with objective response rates between 10% and 29%.

METHODS

Single-center retrospective review of patients with primary CNS tumors prescribed an FGFR inhibitor between 1/1/2020 and 12/1/2025. Prior treatments, radiographic response, and toxicities were collected and analyzed descriptively.

RESULTS

Nine patients were evaluated. Median age was 55 years (range 19-66), and 5 (56%) patients were female. Tumor type included glioblastoma (5, 56%), pilocytic astrocytoma (3, 33%) and low-grade glioma, not elsewhere classified (1, 11%). FGFR alterations included FGFR1 fusion n=1, FGFR1 mutation n=4, FGFR2 fusion n=1, FGFR3 fusion n=3. Prior treatments included surgical resection (8, 89%), radiation (7, 78%), temozolomide (7, 78%), bevacizumab (3, 33%), TPCV (1, 11%) and regorafenib (1, 11%). Two had no systemic treatment prior to FGFR inhibitor initiation. FGFR inhibitors prescribed included infigratinib (n=1, 11%), pemigatinib (n=4, 44%) and erdafitinib (n=4, 44). Median duration of treatment was 115 days (range 35-271) with 1 patient still on treatment at the time of data collection. Seven patients (78%) achieved stable disease while 2 (22%) had progressive disease. Toxicities included fatigue, visual changes, hyperphosphatemia, and stomatitis. Two patients required discontinuation (fatigue n=1, visual changes n=1) and one required dose reduction (visual changes n=1).

CONCLUSIONS

FGFR inhibitors showed promising results with disease stability in 78% of patients for a median duration of 3.8 months in this heavily pre-treated cohort. Therapy was well tolerated, with fatigue being the most common toxicity.