A single-institution study of the natural history of fibroblast growth factor receptor-altered gliomas

Fibroblast growth factor receptor (FGFR) alterations are potential oncogenic drivers that occur in a subset of patients with gliomas, but the natural history of these tumors is not clearly defined. An understanding of outcomes of FGFR-driven glioma has implications for targeted drug development for FGFR inhibitors, which are approved for other cancers.

We performed a retrospective cohort study of patients with gliomas who harbored FGFR alterations, including fusions, single nucleotide variant (SNV), and copy number variant (CNV) alterations seen at Massachusetts General Hospital between 2003 and 2023. The electronic medical record was searched to identify additional molecular data, treatment, and MRI scans. Kaplan-Meier analysis was used to assess progression-free and overall survival (OS).

Thirty-one patients with glioblastoma (GBM), diffuse astrocytoma, and glioneuronal tumors with FGFR alterations were identified: 17 with FGFR fusions, 10 with SNV, and 4 with CNV. FGFR3-TACC3 was the most common fusion in patients with GBM or diffuse astrocytoma. Median OS in patients with GBM was 2.75 years, despite 55% of tumors having an unmethylated MGMT promoter. There were no clearly co-occurring mutations with an FGFR alteration. Of 7 patients who underwent subsequent surgery, 6 lost the original FGFR alteration. No patient received an FGFR inhibitor.

While FGFR alterations are rare in glioma, patients with FGFR-altered GBM may have prolonged survival, which has implications for clinical trial design. We found loss of FGFR alteration at the time of subsequent surgery, raising concern for the therapeutic potential of FGFR-targeting agents in recurrent gliomas.