Multikinase inhibitors for the treatment of radioiodine refractory thyroid cancer: what have we learned from the 'real-world' experience?

Purpose of review Several molecularly targeted drugs for treating radioiodine resistant differentiated thyroid carcinomas (RAIR-DTC) have been identified. Among these, sorafenib and lenvatinib have been approved for clinical use in many countries. The present review will analyze efficacy and safety 'real-world' data (RWD) emerging after their commercialization. Recent findings RWDs confirmed sorafenib and lenvatinib efficacy in terms of progression-free survival and, perhaps, overall survival improvement in patients with RAIR-DTC. Lenvatinib performance in RWDs appeared somehow lower than in randomized clinical trials (RCT), probably because the decision to start treatment in 'real life' was made when patients were in worse clinical conditions than in RCTs. Concerning safety, RWD studies corroborated RCT evidence of elevated overall and serious adverse event incidence. Notably, adverse events were manageable in most cases with appropriate treatment or dose reduction/interruption, so that the need for definitive withdrawal was limited. The suitability of multikinase inhibitors (MKI) as salvage therapy in RAIR-DTCs was also confirmed by RWD experience, at least for lenvatinib in the second-line setting. RWD analysis has corroborated RCT results in terms of MKI efficacy for both first-line and salvage treatment in patients with RAIR-DTC. The safety profiles emerging from RWDs seem to justify the caution recommended by most scientific guidelines.