Table 2.

Overview of the three pivotal phase 3 trials for cabozantinib, sorafenib, and lenvatinib.

Title	Design	Number of Participants	Doses and Cycles	Results	Status
A Study of Cabozantinib Compared with Placebo in Subjects with Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior VEGFR-targeted Therapy (COSMIC-311 Trial) NCT03690388 [54]	Interventional, randomized, double blind	Planned 300 Enrolled187	60 mg or 20 mg cabozantinib or placebo equivalent once daily	PFS vs. placebo: median not reached (96% CI 5.7–not estimable) versus 1.9 months (1.8–3.6); hazard ratio 0.22 (96% CI 0.13–0.36; p < 0.0001)	Active, not recruiting
A Double-Blind Randomized Phase III Study Evaluating the Efficacy and Safety of Sorafenib Compared to Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer (DECISISON) NCT0098428 [55,56,57]	Interventional, double blind, randomized	417	Sorafenib 800 mg/day (400 mg every 12 h) Placebo twice daily (approximately every 12 h).	PFS vs. placebo: hazard ratio, 0.59 (95% CI 0.45–0.76); p < 0.0001; median 10.8 vs. 5.8 months	Completed
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer (SELECT) NCT01321554 [37,58,59,60,61,62,63]	Interventional, double blind, randomized	392	Randomization phase: Starting dose—24 mg Lenvatinib orally (two 10 mg tablets and one 4 mg tablet) once daily, continuously, or placebo matching the lenvatinib treatment.	PFS Treatment: 18.3 months Placebo: 3.6 months HR: 0.21 (99% CI: 0.14 to 0.31) ORR Treatment: 64.8% Placebo: 1.5%.	Completed