Complete disappearance of liver metastases in a patient with iodine-refractory differentiated thyroid cancer subjected to sorafenib re-challenge

The tyrosine-kinase inhibitor (TKI) sorafenib is the most studied targeted agent for the treatment of radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). Its specificity for this clinical setting was suggested by the inhibition of the RAF kinases, which are strikingly involved in the development and progression of thyroid cancer. Nevertheless, sorafenib has a multifunctional activity, and is also active on TK-angiogenic receptors, thus inhibiting neoangiogenesis, which is considered crucial for progression of the disease. The phase III trial DECISION has definitively proved efficacy of sorafenib in RAI-refractory DTC, leading to the approval by the Food and Drug Administration. Given that the study cohort included only TKIs naive patients, sorafenib can be fully considered the first-line systemic therapy for this clinical setting. Nevertheless, such treatment is never curative and has a temporally limited effect. To date, clear indications about the management of RAI-refractory DTC patients after the failure of first-line sorafenib are lacking.