Findings indicate that patients with advanced or metastatic radioactive iodine–refractory differentiated thyroid cancer who received apatinib experienced a prolonged survival benefit vs placebo.
A prolonged survival benefit and tolerable safety profile were observed in patients with advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer who were treated with apatinib (Aitan) vs placebo, meeting the primary end point of the phase 3 REALITY trial (NCT03048877).
At the interim analysis, which had a median follow-up of 18.1 months, the median PFS in the apatinib group was 22.2 months (95% CI, 10.91–not reached [NR]) compared with 4.5 months (95% CI, 1.94-9.17) in the placebo group (HR, 0.26; 95% CI, 0.14-0.47; P <.001). The 12-months PFS rate in the apatinib group was 60.3% (95% CI, 40.8%-75.2%) vs 12.4% (95% CI, 3.4%-27.4%) in the placebo group, and the 24-month PFS rates were 37.2% (95% CI, 15.1%-59.7%) and 4.1% (95% CI, 0.3%-17.2%), respectively.
The post-hoc analysis found that apatinib had significantly improved median PFS for those with high baseline thyroglobulin levels of more than 289.4 ng/mL at 20.1 months (95% CI, 7.62-NR) in the apatinib group and 4.0 months (95% CI, 1.91-9.20) in the placebo. In the population with low levels of 289 ng/mL or less, the median PFS was 25.8 months (95% CI, 9.10-NR) in the apatinib group and 7.5 months (95% CI, 0.95-9.33) in the placebo group (HR, 0.27; 95% CI, 0.11-0.47; P = .003).
A total of 92 patients enrolled on the study were randomized to either the apatinib group (n = 46) or the placebo group (n = 46). Most patients were women (60.9%), and the median age was 57.7 years. At the time of data cutoff, 51 PFS events had occurred. At the time of data cutoff, 51 PFS events had occurred. At baseline, 8 patients received previous targeted therapy, and 3 in the apatinib group had underwent prior chemotherapy.
Patients received 500 mg of apatinib per day or the placebo given orally once daily. The treatment was administered until patients experienced disease progression, intolerable toxic effects, withdrawal of consent, or investigators decision. Dose interruptions, reductions, or discontinuations were used following the occurrence of grade 3 or higher adverse effects (AEs).
Additional study findings indicated that the median overall survival was not reached in the apatinib group and 29.9 months (95% CI, 18.96-NR) in the placebo group (HR, 0.42; 95% CI, 0.18-0.97; P = .04). In the apatinib group, the confirmed overall response rate (ORR) was 54.3% (95% CI, 39.0%-69.1%) and the disease control rate (DCR) was 95.7% (95% CI, 85.2%-99.5%) vs 2.2% (95% CI, 0.1%-11.5%) and 58.7% (95% CI, 43.2%-73.0%), respectively.
Investigators observed shrinkage in target lesions in 89 patients. In 25 patients with a confirmed response, the median tumor shrinkage in the apatinib group was 51.7%. Additionally, patients in the apatinib group had a median time to objective response of 1.9 months, and a median duration of response of 22.4 months.
Patients received apatinib for a median duration of 7.8 months and 2.6 for those receiving placebo. Treatment-related AEs (TRAEs) necessitated dose reductions in 17 patients in the apatinib arm, with toxicities including hand-foot syndrome (n = 6), proteinuria (n = 3), and hypertension (n = 2); three patients discontinued treatment. Patients in the placebo group did not require dose reductions, although 3 discontinued because of hematuria, neck pain, and presence of blood in the urine.
All patients experienced AEs in the apatinib group, as well as 42 in the placebo group. The most common grade 3 or higher TRAEs in the apatinib group were hypertension in 16 patients, hand-foot syndrome in 8, proteinuria in 7, and diarrhea in 7.
During the treatment period, no patients died from TRAEs, however, 1 patient did die in the placebo group from non-treatment–related dyspnea.
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. 2022. doi:10.1001/jamaoncol.2021.6268