LBA89 A randomized multicentered phase III study to evaluate apatinib in subjects with locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer

Apatinib, an oral inhibitor of vascular endothelial growth factor receptor 2, showed clinical activity in preliminary studies involving patients (pts) with differentiated thyroid cancer refractory to radioactive iodine (RAIR-DTC). In this phase III, randomized, double-blind, multicenter trial involving pts with progressive RAIR-DTC, eligible pts were randomized (1:1) to either 500 mg apatinib orally once daily or placebo. The primary endpoint was progression-free survival (PFS), secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. The planned sample size was 118 pts, with 90% power to detect a 6.2-month improvement in PFS at a two-sided alpha level of 0.05. A planned interim analysis would be performed when 60% of expected events occurred. Between February 2017 to March 2020, 92 pts from 20 sites were randomized to apatinib (n=46) or placebo (n=46) arms. The pre-planned interim analysis was performed by the independent Data Monitoring Committee (IDMC) in March 2020 upon the occurrence of 61.45% (51/83) PFS events. The median PFS was 22.21 months (95% CI 10.91-Not Reached) in apatinib group, and 4.47 months (95% CI 1.94-9.17) in the placebo group (HR=0.26, 95% CI 0.14-0.47, p<0.0001), and the p-value was less than the prespecified interim efficacy margin (α=0.0085). ORR was 55.56% vs. 2.27%. The median OS was 29.9 months (95% CI 18.96-Not reached) in the placebo arm, and not reached in apatinib arm (HR=0.42, 95% CI 0.18-0.97, p=0.0356). The most frequent treatment-emergent ≥ grade 3 adverse events in two arms were hypertension (34.8% vs 0%), hand-foot syndrome (17.4% vs 0%) and proteinuria (17.4% vs 2.2%).LBA89Table: LBA89 Summary of efficacyApatinib (N=46)Placebo (N=46)Median PFS, months (95%CI)22.21 (10.91- Not Reached)4.47 (1.94-9.17)p-value<0.0001HR (95% CI)0.26 (0.14-0.47)Median OS, months (95%CI)Not Reached (26.25 - Not Reached)29.90 (18.96 - Not Reached)p-value0.0356HR (95% CI)0.42 (0.18-0.97)ORR, n (%)25 (54.35%)1 (2.17%)95% CI39.01% - 69.10%0.06% - 11.53%p-value<0.0001 Open table in a new tab Apatinib significantly prolonged the PFS, OS, and improved ORR in pts with locally advanced or metastatic RAIR-DTC. The toxic effects of apatinib were well tolerated by the management of adverse events.