Introduction
Papillary thyroid carcinoma (PTC) is the most common type of
differentiated thyroid cancer (DTC) in children and adolescents,
accounting for approximately 90% of thyroid cancers in pediatric
patients.1 Unlike adults, pediatric patients with PTC
often present with advanced, metastatic disease but tend to favorably
respond to total thyroidectomy with lymph node dissection followed by
radioactive iodine (RAI) therapy.2 For the subset of
patients who become refractory to RAI treatment or have RAI non-avid
disease, molecularly targeted kinase inhibitors may provide a medical
therapeutic option.1 Furthermore, children with
metastatic or relapsed/refractory PTC frequently harbor clinically
relevant genomic alterations, with RET fusions most commonly
observed.1,3,4 A review of approximately 2000
pediatric patients with PTC revealed RET fusions in 25-30% of
sporadic cases (range 14-55%).1
Selpercatinib (LOXO-292) is a first-in-class, highly selective,
ATP-competitive, small-molecule RET kinase inhibitor. In LIBRETTO-001, a
phase 1/2 clinical trial evaluating selpercatinib in RET -mutant
medullary thyroid cancer and RET fusion-positive thyroid cancer,
79% of 19 adult patients with RET fusion-positive previously
treated thyroid cancer had an objective response with activity seen
across histologic subtypes, with durable antitumor
activity.5 In May 2020, the Food and Drug
Administration granted accelerated approval to selpercatinib for
patients ≥12 years of age with advanced or metastatic RETfusion-positive thyroid cancer who require systemic therapy and are
RAI-refractory when RAI is appropriate.6 Data for
selpercatinib use in pediatrics is less robust, but shows promising
activity in cases of medullary thyroid cancer,7,8CCDC6-RET fusion positive PTC4 and soft tissue
sarcoma,7 with preliminary safety and efficacy seen in
pediatric patients with RET -altered solid tumors enrolled on
LIBERTTO-121.9 Here we report the sustained response
to selpercatinib, despite 2 dose reductions, in a 13-year-old patient
with metastatic PTC harboring a somatic NCOA4-RET fusion.