Two Cases of Papillary Thyroid Carcinoma With QTc Prolongation During Selpercatinib Administration: A Case Report

Selpercatinib (SEL) is a selective RET (rearranged during transfection) inhibitor that has a good safety profile and potent antitumor effects against RET mutation-positive medullary thyroid carcinoma and RET fusion gene-positive thyroid carcinoma, as demonstrated by the LIBRETTO-001 trial. Its major adverse effects include hypertension, hepatic dysfunction, QTc prolongation, hypersensitivity, and interstitial lung disease. In two patients who received the drug at the study center, SEL demonstrated strong antitumor efficacy but induced QTc prolongation, necessitating a dose reduction or treatment interruption. The first case involved a 76-year-old female patient with a history of surgery for papillary thyroid carcinoma who had been referred to our department in 2024 due to difficulty with walking caused by right iliac metastases. The patient regained the ability to walk after SEL administration shrank the tumors, but due to QTc prolongation, the treatment was interrupted, and the dosage was reduced. The second case involved a 54-year-old male patient with papillary thyroid carcinoma and lung metastases who had undergone a total thyroidectomy followed by radioactive iodine therapy in 2019. Subsequently, metastases developed in the intracranial region, bones, liver, muscles, and adrenal glands, leading to the implementation of SEL therapy in September 2024. QTc prolongation occurred on day 14 of treatment. After the treatment was interrupted for one week, the dosage was reduced to 240 mg/day and has been maintained at this level since then. Following this dose adjustment, the liver metastases resolved, and the other metastases decreased in size. No progression was observed at month 14 after the start of the treatment. In the LIBRETTO-001 trial, QTc prolongation of any grade occurred in approximately 16% of patients, with Grade 3 or higher events reported in about 4%. Reports of QTc prolongation associated with SEL therapy for thyroid cancer remain limited. However, QTc prolongation occurred in both of our patients, suggesting that it may represent a clinically relevant concern in selected individuals. Appropriate dose adjustment and careful monitoring may facilitate continued treatment in selected patients.