Table 2.
Summary of Efficacy Results
| Progression-Free Survival | Vandetanib |
Placebo |
HR | OR | 95% CI | P | ||
|---|---|---|---|---|---|---|---|---|
| No. of Events/No. of Patients | % | No. of Events/No. of Patients | % | |||||
| Primary analysis | 73/231 | 51/100 | 0.46 | 0.31 to 0.69 | < .001 | |||
| Predefined sensitivity analyses | ||||||||
| Cox proportional hazards model | 73/231 | 51/100 | 0.46 | 0.32 to 0.68 | < .001 | |||
| Per protocol analysis | 71/215 | 48/91 | 0.45 | 0.30 to 0.68 | < .001 | |||
| Whitehead's method | 73/231 | 51/100 | 0.51 | 0.35 to 0.72 | < .001 | |||
| Excluding data from open-label phase | 64/231 | 59/100 | 0.27 | 0.18 to 0.41 | < .001 | |||
| Investigator RECIST assessments | 101/231 | 62/100 | 0.40 | 0.27 to 0.58 | < .001 | |||
| Secondary efficacy end points | ||||||||
| Objective response rate | 45 | 13 | 5.48 | 2.99 to 10.79 | < .001 | |||
| Disease control rate | 87 | 71 | 2.64 | 1.48 to 4.69 | .001 | |||
| Calcitonin biochemical response rate | 69 | 3 | 72.9 | 26.2 to 303.2 | < .001 | |||
| CEA biochemical response rate | 52 | 2 | 52.0 | 16.0 to 320.3 | < .001 | |||
NOTE. Progression-free survival sensitivity analyses: An HR of < 1 favors vandetanib; all analyses were conducted by using log-rank test, except for Cox model; all analyses used data derived from centralized RECIST assessments, except for analysis based on investigator RECIST assessments; analysis based on investigator RECIST assessments excludes (censors) data from open-label phase since baseline was reset; for analysis excluding open-label phase, progression dates were imputed for patients who had evidence of progressing disease but had not yet reached a RECIST-defined objective progression at the time of entry into the open-label phase; covariates for Cox model were RET mutation status (positive, negative, unknown), calcitonin doubling time (≤ 24 months, > 24 months, unknown), CEA doubling time (≤ 24 months, > 24 months, unknown), number of prior systemic anticancer therapies (≥ 1, 0), response to most recent systemic anticancer therapy (complete response/partial response, stable disease/progressive disease, not evaluable/unknown), and MTC status (hereditary, sporadic/unknown). Secondary efficacy end points: An OR > 1 favors vandetanib.
Abbreviations: CEA, carcinoembryonic antigen; HR, hazard ratio; MTC, medullary thyroid cancer; OR, odds ratio; RECIST, Response Evaluation Criteria in Solid Tumors; RET, rearranged during transfection.