The Use of Selpercatinib in Recurrent Medullary Thyroid Carcinoma with the RET p.C630R Mutation: A Clinical Case

Abstract

Medullary thyroid carcinoma (MTC) is a rare malignant tumor arising from parafollicular C cells and accounts for 1–5% of all thyroid cancers. Somatic RET mutations occur in 40–50% of sporadic cases and represent targets for selective RET inhibitors. Selpercatinib (RETEVMO, Eli Lilly), approved by the FDA in 2020 and the EMA in 2021, is currently not registered in Kazakhstan. This study describes its successful use in a 74-year-old patient with recurrent MTC, cervical lymph node and lung metastases, vandetanib intolerance, and a confirmed RET p.C630R mutation. Diagnostic evaluation included histology, immunohistochemistry, next-generation sequencing (NGS), contrast-enhanced CT, MRI, ¹⁸F-FDG PET/CT, and laboratory monitoring of calcitonin, carcinoembryonic antigen, thyroid hormones, and liver and kidney function. NGS identified an activating RET p.C630R mutation with an allele frequency of 21.14%. Vandetanib was discontinued because of Quincke’s edema, drug-induced liver injury, and Stevens–Johnson syndrome. Selpercatinib was subsequently administered at a dose of 160 mg/day. After three months, PET/CT performed on March 4, 2026, showed no evidence of local recurrence and an approximately twofold decrease in the metabolic activity of the pulmonary lesions. Calcitonin levels remained stable near the upper limit of normal (16.0–16.3 pg/mL). No adverse events requiring treatment discontinuation were reported, while liver and kidney function remained normal. This case demonstrates the efficacy and favorable tolerability of selpercatinib in RET-positive MTC following intolerance to a first-generation multikinase inhibitor and supports its registration and improved accessibility in Kazakhstan.