In:
Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii50-ii50
Kurzfassung:
Oncogenic driver alterations in fibroblast growth factor receptors (FGFRs) are present in a subset of pediatric gliomas. Debio1347 is an orally available, highly selective FGFR 1–3 inhibitor with a favorable safety profile and encouraging preliminary clinical activity in an adult phase 1 study. METHODS We treated five children with progressive/refractory CNS tumors harboring an FGFR gene alteration with Debio1347 on single patient use protocols. Patients were treated using the 20 mg tablet formulation at the adult recommended phase 2 dose (80 mg/1.73 m2 ′ BSA once daily). RESULTS All adverse events (AEs) were grade 1–2. Most common treatment-related AEs were hyperphosphatemia, ALT elevation and hypoalbuminemia. Two patients met criteria for partial response and two patients had stable disease. A 13-month-old patient with a spinal cord high-grade glioma harboring two FGFR1 mutations had tumor reduction of 96.3% maintained for 11 months. A 26 month-old patient with a pilomyxoid astrocytoma harboring an FGFR1-TACC1 fusion had a tumor reduction of 74.5% maintained for 9 months. Prolonged disease stabilization and clinically significant improvement in visual function was noted in an eight year-old patient with metastatic suprasellar pilomyxoid astrocytoma harboring two FGFR1 mutations (14 months overall and sustained for 6 months off therapy) and in a 14 year-old patient with posterior fossa glioneuronal tumor harboring an FGFR3-TACC3 fusion (26 months and ongoing). CONCLUSIONS FGFR targeted therapy with Debio1347 demonstrated tolerable toxicity and promising anti-tumor efficacy in pediatric patients with recurrent/refractory FGFR altered gliomas. Further studies in this population are warranted.
Materialart:
Online-Ressource
ISSN:
1522-8517
,
1523-5866
DOI:
10.1093/neuonc/noaa215.200
Sprache:
Englisch
Verlag:
Oxford University Press (OUP)
Publikationsdatum:
2020
ZDB Id:
2094060-9
