Abstract: Background and purpose: Radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) is a big challenge in the management of thyroid cancer. Sorafenib and lenvatinib are the 2 tyrosine kinase inhibitors (TKIs) recently approved by FDA, which could not be affordable for most of the Chinese patients. This pilot study aimed to evaluate the short term efficacy and safety of apatinib, a Chinese domestic TKI targeted vascular endothelial growth factor receptor (VEGFR), in advanced RAIR-DTC. Methods: Ten patients who were identified as progressive RAIR-DTC were enrolled in this study. Patients received oral apatinib 750 mg once daily. Both thyroglobulin (Tg) and/or Tg antibody (TgAb) levels were monitored every 2 weeks after the treatment. Computed tomography (CT) was performed every 4 weeks after apatinib treatment to evaluate the response according to response evaluation criteria in solid tumor version 1.1 (RECIST 1.1). Within 8 weeks after apatinib treatment, therapeutic response was evaluated in terms of Tg, a sensitive biochemical tumor marker for DTC, and RECIST 1.1 assessment. Meanwhile, the adverse events (AE) were monitored during the therapy. Results: The Tg levels declined after the first 2 weeks of apatinib treatment, and a mean decline rate of 68% could be observed in 8 patients with Tg available for evaluation after 8 weeks, which repre-sented a biochemical partial response. Eighteen target lesions (TL) of 10 patients were evaluated and followed up. The diameter of TL began to decrease after 4 weeks, and a mean decline of 40% could be observed after 8 weeks’ apatinib treatment. A total of 9 patients (9/10) achieved partial response according to RECIST 1.1 criteria and 1 patient with stable disease, with 90% objective response rate and 100% disease control rate. The most common AE beyond grade 3 included hand-foot-skin reactions, hypertension and hypocalcemia, which accounted for 50%, 30% and 20% of the cases, respectively. No severe AE related to apatinib was observed during the treatment. Conclusion: A safe and rapid response and high partial response rate in terms of biochemistry, RECIST 1.1 could be observed in RAIR-DTC patients within 8 weeks of apatinib treatment.

Key words: Apatinib, Tyrosine kinase inhibitors, Radioactive iodine-refractory differentiated thyroid cancer