ESPE Abstracts

Background: Postnatal linear growth is characterized by a steady decline of growth velocity in healthy individuals, with the exception of sex-steroid induced pubertal growth. Pharmacologic interventions in growth disorders are limited to systemic application of growth factors such as growth hormone, and CNP analogues in conditions with FGFR3 overactivation. Tyrosine kinase receptor inhibitors (TKI) represent a heterogenous group of drugs, mostly used for oncologic indications. Erdafitinib, a novel selective FGFR inhibitor has not been assessed in paediatric patients so far. To our knowledge, this is the first description of linear growth acceleration associated with pharmacologic FGFR3 inhibition.

Patients/Methods: We report on two patients with neurooncological conditions featuring an unanticipated growth spurt after initiation of FGFR-inhibition with Erdafitinib. Clinical, radiographic and biochemical data have been assessed to exclude sex-steroid or GH-driven effects.

Results: Both patients received Erdafitinib (2,8-5,2mg/kg/d) due to progressive, non-responsive FGFR-expressing CNS tumour disease at the age of 13.8 / 10.9 years, respectively. Both patients did not reveal clinical or biochemical signs of sex-steroid action at initiation or during treatment with Erdafitinib. Besides known effects of TKI-inhibition, both patients revealed an unanticipated increase in growth velocity (body height +0.7SDS/9months; +0.5SDS/4.5months respectively) associated with onset of Erdafitinib. Clinical examination and biochemical assessment excluded sex-steroid induced effects and alteration in the GH-state. In line with a distinct mechanism of growth promotion, wrist radiographs revealed profound metaphyseal sclerosis without progression of bone age.

Discussion: The observed increase of growth velocity associated with Erdafitinib treatment in our patients points to a potent growth promoting effect of FGFR3 inhibition. While similar strategies are under investigation in patients with FGFR3-activating mutations, we observed this effect even in children with regular skeletal FGFR3 expression. The context of heavily pre-treated paediatric neurooncological patients with severe growth impairment before initiation of Erdafitinib underlines the hypothetical potential of a growth factor and sex steroid independent growth acceleration by selective FGFR3-inhibition. Future studies will reveal if pharmacologic interventions on FGFR3 can complement current treatment strategies for short stature.