Background: Thyroid cancer is the most common type of endocrine neoplasia.
Differentiated thyroid carcinoma (DTC) represents 94% of all thyroid cancer types. Approximately
20% experience local recurrence and 10% distant metastasis. The recurrent
DTC often becomes less differentiated, loses the iodine uptake capability and consequently
loses the radioactive iodine treatment option. Under these circumstances survivability
drops below 10% at 10 years. The treatment options for dedifferentiated thyroid cancers
are extremely limited. This category sometimes referred to as poorly differentiated thyroid
cancer (PDTC), is characterised by a missing response to radioiodine treatment and a remarkably
reduced survivability. Therefore, new drugs have been developed to fill this gap
Methods: The goal of this work is to review the effects and roles of the multikinase inhibitors sorafenib, sunitinb
and lenatinib in thyroid cancer.
Results: The new tyrosine kinase inhibitors (TKIs) aimed to inhibit tumour angiogenesis. Current clinical trials
with novel drugs have shown promising results. A phase III trial (DECISION) of sorafenib in radioiodine
(RAI)-refractory thyroid cancer showed a median progression-free survival (PFS) of 10.8 months in the sorafenib
group, compared to 5.8 months in the placebo group. Sunitinib, another TKI, exhibited significant antitumour
effects in patients with advanced DTC. Nevertheless, treatment with TKIs can lead to the development
of resistance against these anti-angiogenic treatments, partly due to compensatory mechanisms. Lenvatinib, the
recently approved drug for RAI-refractory thyroid cancer, blocks a different receptor than the currently available
drugs. Lenvatinib inhibits fibroblast growth factor receptor (FGFR), as well as other receptors. FGFR plays
a key role in the development of resistance against anti-angiogenic drugs. In a phase III trial (SELECT) on
RAI-refractory DTC, the lenvatinib group showed a PFS of 18.3 months, compared to 3.6 months in the placebo
group. This led to the approval of lenvatinib, the first drug capable of reversing anti-angiogenic mechanisms.
Conclusion: The frequently adverse effects seen in TKI treatment require further investigation. A well-adjusted
balance between efficacy and adverse effects is desirable. No effects on overall survival were reported. Therefore,
further studies are required.