Glioblastoma (GB) is the most common brain malignancy and accounts for over 50% of all high-grade gliomas. Radiotherapy (RT) with concomitant and adjuvant temozolomide (TMZ) chemotherapy is the current standard of care for patients with newly diagnosed GB up to age 70. Recently, a new standard of care has been adopted for elderly patients (≥ 65 years) based on short course of RT and TMZ. Several clinically relevant molecular markers that assist in diagnosis and prognosis have recently been identified. The treatment for recurrent GB is not well defined, and decision-making is usually based on prior strategies as well as several clinical and radiological factors. The presence of neurologic deficits and seizures can significantly impact quality of life.

PURPOSE: Fibroblast growth factor receptor (FGFR) genomic alterations (amplification, mutations, and/or fusions) occur in ~8% of gliomas, particularly FGFR1 and FGFR3. We conducted a multicenter open-label single-arm phase II study of a selective FGFR1-3 inhibitor, infigratinib (BGJ398), in patients with FGFR-altered recurrent gliomas. EXPERIMENTAL DESIGN: Adults with recurrent/progressive gliomas harboring FGFR alterations received oral infigratinib 125 mg on days 1-21/28 days. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate by Response Assessment in Neuro-Oncology (RANO) criteria. Comprehensive genomic profiling was performed on available pre-treatment archival tissue to explore additional molecular correlations with efficacy. RESULTS: Among 26 patients, the 6-month PFS rate was 16.0% (95% CI 5.0-32.5), median PFS was 1.7 months (95% CI 1.1-2.8), and objective response rate was 3.8%. However, 4 patients had durable disease control lasting longer than 1 year: among these, 3 had tumors harboring activating point mutations at analogous positions of FGFR1 (K656E) [n=2] or FGFR3 (K650E) [n=1] in pre-treatment tissue; an FGFR3-TACC3 fusion was detected in the other. Hyperphosphatemia was the most frequently reported treatment-related adverse event (all-grade, 76.9%; grade 3, 3.8%) and is a known on-target toxicity of FGFR inhibitors. CONCLUSIONS: FGFR inhibitor monotherapy with infigratinib had limited efficacy in a population of patients with recurrent gliomas and different FGFR genetic alterations, but durable disease control lasting more than 1 year was observed in patients with tumors harboring FGFR1 or FGFR3 point mutations or FGFR3‑TACC3 fusions. A follow-up study with refined biomarker inclusion criteria and centralized FGFR testing is warranted.

and Novartis; and has served as local and national principal investigator for trials within his US Oncology research network. Any research payments go toward costs to conduct the research. J.L. Passos-Coelho reports honoraria from Roche, Novartis, and Pfizer; consulting/advisory roles for Roche, Novartis, and Pfizer; research funding from BMS; and travel and accommodation expenses from Roche and Astellas. M. Gil-Gil reports honoraria from Roche, Pfizer, Novartis, and Pierre Fabre; consulting/advisory roles for Daiichi Sankyo, Pfizer, and Novartis; and travel and accommodation expenses from Daiichi Sankyo and Roche. B. Bermejo reports speakers bureau for Novartis, Celgene, and Roche, and travel and accommodation expenses from Pfizer. D.A. Patt reports employment with Texas Oncology, McKesson Specialty Health (self), and Mednax (husband); leadership for Texas Oncology-EVP (self) and Mednax (husband-National Medical Director, Pediatric Cardiology); and stock in Mednax (husband). E. Ciruelos reports consulting/advisory roles for Roche, Novartis, Lilly, and Pfizer (self and immediate family member); speakers bureau for Roche, Novartis, Lilly, and Pfizer; and travel and accommodation expenses from Roche and Pfizer. P. Villagrasa reports honoraria from NanoString Technologies and is a cofounder of Reveal Genomics. E. Petricoin reports leadership positions with