Table 1.
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