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.