A small trial showed that selpercatinib (LOXO-292) is effective in the treatment of medullary thyroid carcinoma (MTC) in children with multiple endocrine neoplasia type 2 (MEN2) and resulted in clinical, biochemical, and radiological improvements. Results were published in the European Journal of Cancer.

By the third month of treatment with selpercatinib, all children (n=6) had complete resolution of clinical symptoms and had gained weight. Calcitonin and carcinoembryonic antigen (CEA) levels had reduced significantly by 4 weeks and continued to decrease over time in all patients, with calcitonin falling more rapidly than CEA.

Patients with radiological evidence of disease (n=5) showed decreases in metastatic disease at 4 weeks which continued to improve at 3 months. Responses to treatment were ongoing at a median follow-up of 13 months (range, 11-22 months) with 4 patients having completed 1 year of treatment.

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Adverse reactions reported in the study included grade 1 or 2 elevation of alanine transferase levels (n=4), serum bilirubin (n=3), or constipation (n=2). No clinically significant treatment-related toxicities were reported.

“Selpercatinib has shown excellent therapeutic efficacy with minimal toxicity in children with MEN2 and progressive metastatic RET-mutated MTC,” the authors reported.

Prior to treatment with selpercatinib, all patients had undergone total thyroidectomy within 3 months of diagnosis with MTC. A total of 4 children had MEN2B caused by de novo mutations in the M918T exon 16 of the RET proto-oncogene. The other 2 children, siblings, had MEN2A caused by Val 804M mutations in RET exon 14.

The children were given starting doses of selpercatinib of 92 mg/m2/dose orally, twice per day.

Selpercatinib is a small-molecule RET-selective tyrosine kinase inhibitor that has been previously trialed in adults. All patients were provided treatment as part of a compassionate Named Patient Programme, as they were too young to participate in the LIBRETTO 531 trial (NCT04211337) that is comparing selpercatinib to cabozantinib and vandetanib.


Shankar A, Kurzawinski T, Ross E, et al. Treatment outcome with a selective RET tyrosine kinase inhibitor selpercatinib in children with multiple endocrine neoplasia type 2 and advanced medullary thyroid carcinoma. Eur J Cancer. 2021;158:38-46. doi:10.1016/j.ejca.2021.09.012