Hypercalcemia as a rebound phenomenon of LOXO 292 efficacy in Medullary Thyroid Cancer.

Abstract Medullary thyroid cancers (MTC) are neuroendocrine tumors of thyroid parafollicular C cells; calcitonin is the most common secreted hormone. Sporadic or hereditary RET gene mutation is a common cause of MTC. LOXO-292 is a highly selective RET tyrosine kinase inhibitor. Here we present a case of a 57-year-old male patient with metastatic MTC harboring a RET M918T mutation with high levels of calcitonin that received LOXO-292 160 mg orally twice daily. The patient developed abrupt shrinkage of his disease and rapidly declining calcitonin levels, as well as, hypercalcemia during the first two weeks, conceivably caused by a secondary rebound mechanism. This phenomenon could be related to a rapid decrease in calcitonin levels suggesting that a close monitoring of calcium levels is advised while treating MTC with LOXO-292 especially in the first 2 weeks.