Medication Summary
Although surgery remains the standard treatment for medullary thyroid carcinoma (MTC), several tyrosine kinase inhibitors (TKIs) are approved by the US Food and Drug Administration (FDA) for treatment of advanced or metastatic MTC. These include the multitarget TKIs vandetanib and cabozantinib, and the RET tyrosine kinase inhibitors selpercatinib and pralsetinib. (See Treatment)
Tyrosine Kinase Inhibitors
Class Summary
These agents target various tyrosine kinases including MET, RET, and VEGFR-2.
Vandetanib (Caprelsa)
Tyrosine kinase inhibitor (TKI) with selective activity against RET, VEGFR-2, and EGFR. Indicated for treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.
Cabozantinib (Cometriq)
Cabozantinib is a tyrosine kinase inhibitor that targets RET, MET, VEGFR-1, -2, and -3, KIT, TrkB, FLT-3, AXL, and TIE-2 pathways; these tyrosine kinases are involved in both normal cellular function and pathologic processes (eg, oncogenesis, metastasis, tumor angiogenesis, and maintenance of tumor microenvironment). It is indicated for treatment of progressive, metastatic medullary thyroid cancer.
RET Kinase Inhibitors
Class Summary
Genomic alterations in rearranged during transfection (RET) kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth.
Selpercatinib (Retevmo)
Selpercatinib is a kinase inhibitor of wild-type rearranged during transfection (RET) and multiple mutated RET isoforms, as well as vascular endothelial growth factor receptors (VEGFR1, VEGFR3). It is indicated for advanced or metastatic RET-mutant MTC in adults and children aged 12 years or older who required systemic therapy.
Pralsetinib (Gavreto)
A once-daily therapy designed to selectively target RET alterations. Indicated for advanced or metastatic rearranged during transfection (RET)-mutant MTC in adult and pediatric patients ≥12 years who require systemic therapy, or with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).
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Algorithm for the management of a solitary thyroid nodule. FNAB = fine needle aspiration biopsy; US = ultrasonography.
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MRI of a patient with medullary thyroid carcinoma.
Tables
Risk Level |
RETcodon Mutation |
Possible Diagnoses |
Prophylactic Thyroidectomy Recommendations |
Follow-up |
Highest Risk (HST) |
M918T+All MEN2B |
MEN2B |
Within the first year of life or the first months of life based upon specialist and parental discussions. The ability to identify and preserve or transplant parathyroid glands determines level VI dissection. |
Physical exam, neck US, serum Ctn, and serum CEA every 6 mos first year, then annually; begin screening for pheochromocytoma at age 11 yr |
High Risk (H) |
C634, A883F |
MEN2A |
At or before age 5 yr, to be determined on the basis of serum Ctn |
Physical exam, neck US, serum Ctn, and serum CEA every 6 mos first year, then annually. Begin screening for pheochromocytoma at age 11. |
Moderate Risk (MOD) |
All other mutations |
MEN2A |
When serum Ctn becomes elevated or in childhood to avoid lengthy evaluation period. |
Evaluate every 6 months for 1 year. Annual follow-ups thereafter if serum Ctn is normal or undetectable. Begin screening for pheochromocytoma at age 16 yr |
