Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations: A Multicenter Phase II Study
Year: 2022
Type: article
Study design: Clinical Trial
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. 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. 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. 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.
Source: Clinical Cancer Research
Authors: Andrew B. Lassman, Juan Manuel Sepúlveda-Sánchez, Timothy F. Cloughesy, Miguel J. Gil-Gil, Vinay K. Puduvalli, Jeffrey J. Raizer, Filip Y.F. De Vos, Patrick Y. Wen, Nicholas A. Butowski, Paul M.J. Clement, Morris D. Groves, Cristóbal Belda-Iniesta, Pierre Giglio, Harris S. Soifer, Steven Rowsey, Cindy Xu, Francesca Avogadri, Ge Wei, Susan Moran, Patrick Roth
Institutions: Herbert Irving Comprehensive Cancer Center, Columbia University, Hospital Universitario 12 De Octubre, University of California, Los Angeles, Institut Català d'Oncologia, The Ohio State University Wexner Medical Center, The Ohio State University, Northwestern University, Utrecht University, University Medical Center Utrecht, Center for Neuro-Oncology, Dana-Farber Cancer Institute, University of California, San Francisco, KU Leuven, Hospital Universitario HM Sanchinarro, University of Zurich, University Hospital Zurich
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4220760248