Advanced Thyroid Cancer: Systemic Therapy

Advanced Thyroid Cancer: overview

This algorithm addresses systemic therapy for advanced thyroid cancer, with the first branch point being histologic type. For radioiodine-refractory differentiated thyroid cancer (DTC), the VEGFR tyrosine kinase inhibitors lenvatinib (SELECT) and sorafenib (DECISION) are shown, along with selpercatinib for RET-altered tumors (LIBRETTO-001) and dabrafenib plus trametinib for BRAF-mutant tumors (ROAR). DECISION showed that sorafenib improved progression-free survival versus placebo in radioiodine-refractory DTC and was the first targeted therapy approved in this setting.

For medullary thyroid cancer (MTC), RET-directed therapy with selpercatinib or pralsetinib (LIBRETTO) is one option, and the RET-independent multikinase inhibitors cabozantinib or vandetanib (EXAM / ZETA) are the other. Anaplastic thyroid cancer (ATC) is treated as an aggressive disease: dabrafenib plus trametinib is used for BRAF V600E-mutant tumors, and chemoradiation or a clinical trial for other patients. The organizing principle is that molecular testing directs targeted therapy, with the relevant alterations (RET, NTRK, BRAF) differing by histology.

Trials behind this algorithm

• SELECT trial, Lenvatinib 2nd line Schlumberger et al, NEJM, 2015, PMID: 25671254
• DECISION Brose MS et al, Lancet, 2014; PMID: 24768112
• LIBRETTO-001 (thyroid) Wirth LJ et al, JCO, 2024; PMID: 39094065
• ROAR ATC Subbiah V et al, Ann Oncol, 2022; PMID: 35026411

Background reading: Thyroid cancers board review notes.