Abstract
INTRODUCTION: Growth acceleration during postnatal growth only occurs during puberty as a physiological event and during catch-up growth mediated by growth-promoting therapies in growth disorders. Here we report on novel observations of skeletal symptoms during treatment with erdafitinib, a tyrosine kinase inhibitor (TKI) prescribed on the basis of a compassionate-use program. METHODS: Analysis of anthropometric, biochemical, clinical, and radiographic data of patients with CNS tumors who revealed an unanticipated growth spurt with initiation of therapy with erdafitinib was performed retrospectively. RESULTS: Linear growth acceleration was independent of sex steroids and IGF1 levels, which is especially remarkable in the context of heavily pretreated pediatric neuro-oncology patients with severe growth impairment before initiation of therapy. Growth acceleration was accompanied by a distinct widening of the growth plate and enhanced metaphyseal mineralization shortly after the start of TKI therapy. CONCLUSIONS: While targeted therapies including TKIs have become an essential part of adult cancer treatment, applications in children are still limited. Off-target effects specific to the pediatric population have been observed in various organ systems; however, knowledge about the effect of TKIs on the growing skeleton is scarce. Treatment with erdafitinib inhibits FGFR3-mediated effects and thus represents a very logical hypothetical framework of growth factor and sex steroid-independent growth acceleration.