Radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) is a big challenge in the management of thyroid cancer. Sorafenib and lenvatinib are the 2 FDA-approved tyrosine kinase inhibitors (TKIs), which might not be affordable for most of the Chinese patients (pts). Apatinib is an oral TKI targeting VEGFR-2, with a patient assistance program available in China. It achieved a quick Tg decline of 21% 2 weeks later and an objective response rate (ORR) of 90%, showing promising efficacy in RAIR-DTC (Lin et al, ATA 2016, Short Call Poster 65; Lin et al, Oncotarget, Epub Feb. 02, 2017). Thus, this study aimed to further evaluate the efficacy and safety of apatinib in treating RAIR-DTC.
This study is a multicentre, randomised, double-blind, parallel-group, placebo-controlled, phase III trial in China. Adult pts with locally advanced or metastatic RAIR-DTC are eligible. The inclusion criteria include at least one measurable lesion; disease progression within the past 12 months; and ECOG PS 0–2. Pts are defined as RAIR-DTC if they have target lesion(s) without iodine uptake, received one RAI treatment (≥3.7 GBq [≥100 mCi]) but progressed within the past 12 months, received two RAI treatments or more with a time interval of less than 12 months and progressed at least 12 months later), or received cumulative RAI activity over 22.2 GBq (≥600 mCi). Previous targeted therapy is not allowed. Enrolled patients will be randomly assigned to receive apatinib (500 mg qd) and placebo, respectively. Four weeks is defined as one cycle. Dose increase to 750 mg and dose reduction to 250 mg are allowed. The primary endpoint is progression free survival. The secondary endpoints include disease control rate, ORR, duration of response, changes in serum Tg and TgAb concentration, quality of life, and safety. A multiple Cox proportional hazards model is used to evaluate the hazard ratios after adjusting iodine uptake, metastatic lesion site, gender, and age. 118 pts will be recruited assuming a 106.9% increase in median PFS in the apatinib arm compared with the placebo arm. As of 2nd May 2017, 3 eligible patients have been enrolled.
Clinical trial identification
NCT03048877 (Release date: February 7, 2017)
Legal entity responsible for the study
All authors have declared no conflicts of interest.