Table 1.

Phase 3 Clinical Trials of Kinase Inhibitors in Patients with Differentiated or Medullary Thyroid Carcinoma.^*

Drug and Trial	No. of Patients		Tumor	Progression-free Survival				Dose-Related Events in Active-Drug Group	Deaths in Active-Drug Group
	Active Drug	Placebo		Active Drug	Placebo	Hazard Ratio (95% CI) †	P Value
				mo				% of patients	no.
Sorafenib (DECISION)45	207	210	DTC	10.8	5.8	0.59 (0.45–0.76)	<0.001	64 had dose reduced, and 18 discontinued	12, with 1 considered to be drug related
Lenvatinib (SELECT)46	261	131	DTC	18.3	3.6	0.21 (0.14–0.31)	<0.001	68 had dose reduced, and 14 discontinued	20, with 6 considered to be drug related
Vandetanib (ZETA)47	231	100	MTC	30.5	19.3	0.46 (0.31–0.69)	<0.001	35 had dose reduced, and 12 discontinued	5, with 1 considered to be drug related
Cabozantinib (EXAM)48	219	111	MTC	11.2	4.0	0.28 (0.19–0.40)	<0.001	79 had dose reduced, and 22 discontinued	12, with 9 considered to be drug related

^*DECISION was a multicenter, randomized, double−blind, placebo−controlled phase 3 trial of sorafenib in patients with radioactive iodine–refractory locally advanced or metastatic, progressive, differentiated thyroid cancer,⁴⁵ SELECT a phase 3, randomized, double−blind, multicenter trial of lenvatinib, as compared with placebo, in patients with progressive differentiated thyroid cancer that is refractory to iodine−131,⁴⁶ ZETA a phase 3 prospective, randomized, double−blind, trial of vandetanib, as compared with placebo, in patients with locally advanced or metastatic medullary thyroid cancer,⁴⁷ and EXAM a phase 3 prospective, randomized, double−blind, trial of cabozantinib, as compared with placebo, in patients with progressive advanced medullary thyroid cancer.⁴⁸ Progression−free survival was the primary end point in each of the four trials. Outcome comparisons of these trials should be done with caution because there were differences in trial design and eligibility criteria. CI denotes confidence interval, DTC differentiated thyroid carcinoma, and MTC medullary thyroid carcinoma.

^†The hazard ratio is for disease progression or death. A 99% confidence interval was used for the hazard ratio in the SELECT trial.⁴⁶