TY - JOUR
T1 - Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations
T2 - A Multicenter Phase II Study
AU - Lassman, Andrew B.
AU - Sepúlveda-Sánchez, Juan Manuel
AU - Cloughesy, Timothy F.
AU - Gil-Gil, Miguel J.
AU - Puduvalli, Vinay K.
AU - Raizer, Jeffrey J.
AU - De Vos, Filip Y.F.
AU - Wen, Patrick Y.
AU - Butowski, Nicholas A.
AU - Clement, Paul M.J.
AU - Groves, Morris D.
AU - Belda-Iniesta, Cristóbal
AU - Giglio, Pierre
AU - Soifer, Harris S.
AU - Rowsey, Steven
AU - Xu, Cindy
AU - Avogadri, Francesca
AU - Wei, Ge
AU - Moran, Susan
AU - Roth, Patrick
N1 - Publisher Copyright:
© 2022 The Authors.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-21-2664
DO - 10.1158/1078-0432.CCR-21-2664
M3 - Article
C2 - 35344029
AN - SCOPUS:85128466513
SN - 1078-0432
VL - 28
SP - 2270
EP - 2277
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 11
ER -