In an interim analysis of the Chinese phase III REALITY trial reported in JAMA Oncology, Lin et al found that apatinib, a highly selective VEGFR2 inhibitor, significantly prolonged progression-free survival vs placebo in patients with progressive, locally advanced or metastatic, radioactive iodine–refractory differentiated thyroid cancer.

Study Details

In the multicenter double-blind trial, 92 patients were randomly assigned between February 2017 and March 2020 to receive apatinib at 500 mg daily (n = 46) or placebo (n = 46) until disease progression or unacceptable toxicity. Patients with disease progression on placebo were permitted to cross over to receive apatinib.

The primary endpoint was investigator-assessed progression-free survival.

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Progression-Free Survival

Median follow-up was 18.1 months (interquartile range = 12.7–22.2 months). Median progression-free survival was 22.2 months (95% confidence interval [CI] = 10.9 months–not reached) in the apatinib group vs 4.5 months (95% CI = 1.9–9.2 months) in the placebo group (hazard ratio [HR] = 0.26, 95% CI = 0.14–0.47, P < .001; prespecified significance level = .0085). Rates at 12 and 24 months were 60.3% vs 12.4% and 37.2% vs 4.1%, respectively.

Objective response rates were 54.3% vs 2.2% (P < .001) and disease control rates were 95.7% vs 58.7% (P < .001). A total of 35 patients in the placebo group crossed over to receive apatinib. Median overall survival was not reached (95% CI = 26.3 months–not reached) in the apatinib group vs 29.9 months (95% CI = 19.0 months–not reached) in the placebo group (HR = 0.42, 95% CI = 0.18–0.97, P = .04). Rates at 12 and 24 months were 95.4% vs 79.7% and 82.2% vs 59.9%, respectively.

Adverse Events

Grade ≥ 3 adverse events occurred in 78.3% of patients in the apatinib group vs 17.4% of the placebo group, and treatment-related grade ≥ 3 adverse events occurred in 73.9% of the apatinib group, most commonly hypertension (34.8%), hand-foot syndrome (17.4%), proteinuria (15.2%), and diarrhea (15.2%). None of these adverse events occurred at grade ≥ 3 in the placebo group. No treatment-related deaths were reported.

The investigators concluded, “The REALITY trial met its primary endpoint of progression-free survival at the prespecified interim analysis. Apatinib showed significant clinical benefits in both prolonged progression-free survival and overall survival with a manageable safety profile in patients with progressive, locally advanced or metastatic, radioactive iodine–refractory differentiated thyroid cancer.”

Yansong Lin, MD, PhD, of the Chinese Academy of Medical Science and Peking Union Medical College, Beijing, and Shukui Qin, MD, PhD, of the Cancer Center of Bayi Hospital, Nanjing Chinese Medicine University, Nanjing, are the corresponding authors for the JAMA Oncology article.

Disclosure: The study was funded by the National Natural Science Foundation of China, National Key Projects of Research and Development Plan, and Jiangsu Hengrui Pharmaceuticals Co Ltd. For full disclosures of the study authors, visit jamanetwork.com.