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Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations: A Multicenter Phase II Study.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2022 Jun 01; Vol. 28 (11), pp. 2270-2277. - Publication Year :
- 2022
-
Abstract
- Purpose: 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.<br />Patients and Methods: Adults with recurrent/progressive gliomas harboring FGFR alterations received oral infigratinib 125 mg on days 1 to 21 of 28-day cycles. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate by Response Assessment in Neuro-Oncology criteria. Comprehensive genomic profiling was performed on available pretreatment archival tissue to explore additional molecular correlations with efficacy.<br />Results: Among 26 patients, the 6-month PFS rate was 16.0% [95% confidence interval (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 pretreatment 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.<br />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.<br /> (©2022 The Authors; Published by the American Association for Cancer Research.)
- Subjects :
- Adult
Follow-Up Studies
Humans
Microtubule-Associated Proteins
Phenylurea Compounds
Protein Kinase Inhibitors adverse effects
Pyrimidines
Receptor, Fibroblast Growth Factor, Type 3 genetics
Glioma drug therapy
Glioma genetics
Neoplasm Recurrence, Local drug therapy
Neoplasm Recurrence, Local genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 28
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 35344029
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-21-2664