Abstract
OBJECTIVE: Sorafenib and lenvatinib have been recommended as standard tyrosine kinase inhibitors (TKIs) for progressive radioiodine-refractory differentiated thyroid carcinoma (RR-DTC). However, their efficacy remains limited with unresolved drug resistance. Therefore, we conceived this open-label study based on real-world evidence to investigate the efficacy and safety of apatinib in patients with progressive RR-DTC. METHODS: Off-label use of apatinib as either initial treatment or salvage treatment for sorafenib resistance was investigated. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. RESULTS: For all 28 enrolled patients, the median PFS was 15.1 months, with an ORR of 69.6%. The median OS was not reached at the data cut-off. In detail, the median PFS of 17.3 months and the ORR of 75% were determined in patients with TKI-naive RR-DTC (initial treatment group, n = 14). And, in patients with first-line sorafenib-resistant RR-DTC (salvage treatment group, n = 14), a median PFS of 12.0 months was reached, with an ORR of 45.5%. In the salvage treatment group, the median OS from the start of apatinib administration was 20.6 months, reaching 89.1 months from sorafenib treatment initiation. Adverse events at grade 3 or higher occurred in 64.3% of all subjects treated with apatinib. CONCLUSIONS: This study demonstrated that apatinib shows promise against RR-DTC with tolerable toxicity, representing a novel initial treatment for progressive RR-DTC and effective salvage treatment for RR-DTC resistant to sorafenib.