Apatinib improved survival outcomes, compared with placebo, in patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC), according to results of a trial published in JAMA Oncology

In the phase 3 REALITY trial (ClinicalTrials.gov Identifier: NCT03048877), researchers evaluated the efficacy and safety of apatinib in patients with progressive locally advanced or metastatic RAIR-DTC.

The study enrolled 92 patients, with a mean age of 58 years, from 21 sites in China. Patients were randomly assigned 1:1 to receive apatinib (500 mg) or placebo once daily until disease progression, intolerable toxicity, consent withdrawal, or the investigators decided to discontinue treatment.

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Patients in the placebo arm could cross over to the apatinib arm after disease progression. Ultimately, 35 patients crossed over to apatinib from placebo, and 11 patients in the apatinib arm continued on apatinib after progression.

The median duration of treatment was 7.8 months in the apatinib arm and 2.6 months in the placebo arm.

The objective response rate (ORR) was 54.3% in the apatinib arm and 2.2% in the placebo arm (P <.001). All responses were partial responses. The median time to response in the apatinib arm was 1.9 months, and the median duration of response was 22.4 months.

Among patients who crossed over from placebo to apatinib, the ORR was 51.4%. Among the 11 patients who continued on apatinib after progression, 5 achieved stable disease.

At a median follow-up of 18.1 months, the  median progression-free survival (PFS) was significantly longer in the apatinib arm than in the placebo arm — 22.2 months and 4.5 months, respectively (hazard ratio [HR], 0.26; 95% CI, 0.14-0.47; P <.001).

Apatinib significantly improved PFS in patients with high baseline thyroglobulin levels (>289.4 ng/mL; HR, 0.23; 95% CI, 0.09-0.47; P <.001) and low baseline thyroglobulin levels (≤289 ng/mL; HR, 0.27; 95% CI, 0.11-0.47; P =.003).

The median overall survival (OS) was superior in the apatinib arm. The median OS was not reached in the apatinib arm and was 29.9 months in the placebo arm (HR, 0.42; 95% CI, 0.18-0.97; P =.04).

In the apatinib arm, 37.0% of patients had a dose reduction due to treatment-related adverse events (AEs) of any grade. The most common grade 3 or higher treatment-related AEs in the apatinib arm were hypertension (34.8%), hand-foot syndrome (17.4%), proteinuria (15.2%), and diarrhea (15.2%). There were no treatment-related deaths.

Based on these results, the researchers concluded that “apatinib might provide a new treatment option for patients with radioactive iodine-refractory differentiated thyroid cancer.”

Disclosures: This research was partially supported by Jiangsu Hengrui Pharmaceuticals Co Ltd. Three study authors were employed by the company at the time of the study. Please see the original reference for a full list of disclosures.


Lin Y, Qin S, Li Z, et al. Apatinib vs placebo in patients with locally advanced or metastatic, radioactive iodine-refractory differentiated thyroid cancer: The REALITY randomized clinical trial. JAMA Oncol. Published online December 16, 2021. doi:10.1001/jamaoncol.2021.6268