Accelerated linear growth during Erdafitinib treatment: An FGFR related, but growth factor and sex steroid independent mechanism?

Abstract

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 on skeletal symptoms during treatment with Erdafitinib, a tyrosine kinase inhibitor (TKI) prescribed on the basis of a compassionate-use program. 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. 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 distinct widening of the growth plate and enhanced metaphyseal mineralization shortly after the start of TKI therapy. While targeted therapies including TKIs have become an essential part in 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. As treatment with Erdafitinib inhibits FGFR3-mediated effects and thus represents a very logical hypothetical framework of growth factor and sex steroid independent growth acceleration.