Overview of Thyroid Cancer Treatment
Thyroid cancer treatment varies significantly by histologic subtype. Differentiated thyroid cancer (DTC) refractory to radioactive iodine is treated with multi-kinase inhibitors (lenvatinib, sorafenib, cabozantinib). Medullary thyroid cancer (MTC) benefits from RET-targeted therapy (selpercatinib, vandetanib, cabozantinib). Anaplastic thyroid cancer (ATC) with BRAF V600E mutation responds to dabrafenib + trametinib.
Treatment by Histologic Subtype
Differentiated (DTC) — RAI-Refractory
- Lenvatinib (Lenvima) — multi-kinase inhibitor
- Sorafenib (Nexavar) — multi-kinase inhibitor
Medullary (MTC)
- Selpercatinib (Retevmo) — selective RET inhibitor
- Vandetanib (Caprelsa) — multi-kinase/RET
- Cabozantinib (Cabometyx) — multi-kinase/RET/MET
Anaplastic (ATC) — BRAF V600E
- Dabrafenib + Trametinib (BRAF+MEK combination)
Epidemiology & Impact
Thyroid cancer is the most common endocrine malignancy, with approximately 47,540 new cases expected in 2025. It has one of the highest 5-year survival rates at 98.4% and occurs 3 times more frequently in women. Incidence rose dramatically through 2015 largely due to overdiagnosis of small papillary microcarcinomas, but has since declined with revised guidelines. The four main subtypes are papillary (80%), follicular (10%), medullary (5%, arising from C cells), and anaplastic (2%, among the most aggressive human cancers with median survival under 6 months).
Molecular Biology & Biomarkers
Thyroid cancer subtypes have distinct molecular drivers. Papillary thyroid cancer harbors BRAF V600E (approximately 60%), RAS mutations (15%), and RET/PTC rearrangements (10-20%). Follicular thyroid cancer is driven by RAS mutations and PAX8-PPARG fusions. Medullary thyroid cancer is caused by activating RET point mutations, with germline RET mutations defining MEN2 syndromes requiring prophylactic thyroidectomy. Anaplastic thyroid cancer accumulates additional mutations in TP53, TERT promoter, and PI3K pathway on a background of differentiated thyroid cancer driver mutations, reflecting dedifferentiation.
Evolving Treatment Landscape
Differentiated thyroid cancer (papillary, follicular) is treated with surgery, radioactive iodine (RAI), and TSH suppression, achieving cure rates exceeding 95%. For RAI-refractory disease, lenvatinib and sorafenib are approved multi-kinase inhibitors. The combination of dabrafenib plus trametinib (BRAF plus MEK inhibition) is approved for BRAF V600E-mutated anaplastic thyroid cancer based on remarkable response rates, transforming a previously universally fatal disease. Selpercatinib and pralsetinib target RET-altered thyroid cancers with high response rates. Larotrectinib and entrectinib are approved for the rare NTRK fusion-positive cases. Medullary thyroid cancer is treated with cabozantinib or vandetanib, with selpercatinib showing superior activity in RET-mutant MTC.
Approved Indications (US/FDA)
RET fusion-positive thyroid cancer (age ≥12) requiring systemic therapy, and RET-mutant medullary thyroid cancer (MTC) requiring systemic therapy.
Dosing Schedule
120 mg orally twice daily (<50 kg) or 160 mg twice daily (≥50 kg)
Cycle Length
Continuous daily dosing
Combination Therapy
Monotherapy (selective RET kinase inhibitor)
Approved Indications (US/FDA)
Treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable, locally advanced, or metastatic disease.
Dosing Schedule
300 mg orally once daily
Cycle Length
Continuous daily dosing
Combination Therapy
Monotherapy (multi-kinase inhibitor: VEGFR, EGFR, RET)
Approved Indications (US/FDA)
RET-mutant medullary thyroid cancer requiring systemic therapy, and RET fusion-positive thyroid cancer requiring systemic therapy who are RAI-refractory.
Dosing Schedule
400 mg orally once daily on empty stomach
Cycle Length
Continuous daily dosing
Combination Therapy
Monotherapy (selective RET kinase inhibitor)
Approved Indications (US/FDA)
Treatment of BRAF V600E-mutated anaplastic thyroid cancer (ATC) with no satisfactory locoregional treatment options.
Dosing Schedule
Dabrafenib 150 mg twice daily + trametinib 2 mg once daily
Cycle Length
Continuous daily dosing
Combination Therapy
Combination BRAF + MEK inhibition
Approved Therapies
🇪🇺 European Union / EMA Information
EMA-Approved Therapies for Thyroid Cancer
The European Medicines Agency (EMA) regulates drug approvals across the European Union. Below are key approvals with comparative timelines to FDA, demonstrating regulatory differences between regions.
EMA Approval: May 2015 |
FDA Approval: February 2015
FDA 3 months earlier
Indication: Radioactive iodine-refractory differentiated thyroid cancer
Pivotal Trial: SELECT (EudraCT: 2011-000286-37)
EMA Approval: December 2014 |
FDA Approval: November 2012
FDA 2 years earlier
Indication: Progressive medullary thyroid cancer
Pivotal Trial: EXAM (EudraCT: 2008-005953-30)
📊 Regulatory Observations
- FDA typically approves 3-12 months before EMA for new molecular entities
- Approval gaps have narrowed in recent years for breakthrough therapies
- Dosing regimens generally align between FDA and EMA approvals
- ESMO and NCCN guidelines may differ in sequencing recommendations
- Reimbursement varies significantly across EU member states
For complete European approval details, visit ema.europa.eu ↗
🇪🇺 EU Clinical Pipeline (EudraCT Trials)
Active clinical trials registered in EU Clinical Trials Register
Phase 3 Trials
Late-stage European confirmatory trials
Lenvatinib
Target Population: RAI-refractory DTC
Frequently Asked Questions
FAQ
Is thyroid cancer always serious?
Most thyroid cancers (papillary and follicular types) have excellent prognosis with cure rates exceeding 95%. Many small papillary thyroid cancers are so indolent that active surveillance without immediate surgery is now an accepted option. However, anaplastic thyroid cancer is one of the most lethal cancers with median survival under 6 months.
What is radioactive iodine therapy?
Radioactive iodine (RAI or I-131) exploits the thyroid's unique ability to concentrate iodine. After thyroidectomy, RAI destroys residual thyroid tissue and microscopic cancer. It is effective for differentiated thyroid cancer but not for medullary or anaplastic types, which do not take up iodine.
What targeted therapies are available?
Multiple targeted therapies are now approved: lenvatinib and sorafenib for RAI-refractory differentiated thyroid cancer, dabrafenib-trametinib for BRAF-mutated anaplastic cancer, selpercatinib and pralsetinib for RET-altered cancers, and larotrectinib/entrectinib for NTRK fusion-positive tumors.
Active Clinical Trials
PHASE 3
Late-Stage Pivotal Trials
LIBRETTO-531
Drug: Selpercatinib (RET inhibitor)
Population: RET-mutant medullary thyroid cancer, adjuvant
Status: Ongoing | NCT04211337 ↗
Search for additional trials on ClinicalTrials.gov ↗
PHASE 2
Efficacy and Safety Studies
BRAF/MEK Inhibitors
Drugs: Dabrafenib + Trametinib
Target: BRAF V600E-mutant anaplastic thyroid cancer
Search for additional trials on ClinicalTrials.gov ↗
PHASE 1
First-in-Human Dose-Finding Studies
Phase 1 trials establish safety profiles and determine recommended doses for novel anticancer agents in early-stage development.
Search for active Phase 1 trials on ClinicalTrials.gov ↗
Find Clinical Trials Near You
Interested in participating in a clinical trial? Visit ClinicalTrials.gov to search for trials by location, cancer type, and eligibility criteria. Discuss options with your oncologist to determine if clinical trial participation is appropriate for you.
Search ClinicalTrials.gov →
🇺🇸 US Clinical Pipeline (NCT Trials)
Active clinical trials registered in ClinicalTrials.gov
Phase 3 Trials
Pivotal trials comparing investigational treatments to standard of care
Lenvatinib
Target Population: Radioiodine-refractory DTC
Sorafenib
Target Population: Radioiodine-refractory DTC
Cabozantinib
Target Population: Progressive medullary thyroid cancer
Phase 2 Trials
Mid-stage trials evaluating efficacy and optimal dosing regimens
Selpercatinib
Target Population: RET-altered thyroid cancer
Dabrafenib + trametinib
Target Population: BRAF V600E ATC
Phase 1 Trials
Early-stage trials establishing safety profiles and determining recommended doses
Novel RET inhibitors
Target Population: RET-mutant MTC
NTRK inhibitors
Target Population: NTRK-fusion thyroid
Cabozantinib
Target Population: Medullary thyroid
Phase 2 Trials
Mid-stage European efficacy trials
Selpercatinib
Target Population: RET-altered
BRAF/MEK combos
Target Population: BRAF-mutant
Phase 1 Trials
Early-stage European safety trials
Novel RET inhibitors
Target Population: RET-mutant
Selective TKIs
Target Population: Advanced thyroid