Medical treatment decision-making for advanced medullary thyroid cancer

Medullary thyroid carcinoma (MTC) is rare, accounting for approximately 1-2% of all thyroid cancers. Thyroidectomy is considered the primary treatment for MTC and conveys the highest chance for cure if the disease is detected early. Although typically indolent for most patients, those who demonstrate more rapid progression or symptomatic disease can be treated with either multikinase inhibitors (MKIs), such as cabozantinib and vandetanib, or selective RET inhibitors. The understanding that aberrant RET receptor activation is a primary driver of MTC led to clinical investigations with MKIs primarily targeting vascular endothelial growth factor receptor (VEGFR), as well as RET and other kinase receptors. Selective RET inhibitors demonstrate exciting results in phase I clinical trials for RET-altered cancers, which led to the recent approval by the US Food and Drug Administration of selpercatinib. This chapter uses a case-based approach to answer the questions of when to consider initiating systemic therapy and which agent to use.