r 50 mg SUTENT or placebo orally, once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off (Schedule 4/2) until disease progression or withdrawal from the study for another reason. Treatment was unblinded at the time of disease progression. Patients randomized to placebo were then offered crossover to open-label SUTENT, and patients randomized to SUTENT were permitted to continue treatment per investigator judgment.
The intent-to-treat (ITT) population included 312 patients. Two-hundred seven patients were randomized to the SUTENT arm, and 105 patients were randomized to the placebo arm. Baseline age, gender, race and ECOG performance status were comparable between the placebo and SUTENT groups. Prior exposure to imatinib was similar between the two study arms. Demographics and patient characteristics are shown in Table 4.
Table 4. Baseline Demographics in Study A GIST
SUTENT (n=207) Placebo (n=105)
Gender [N (%)]
Male 132 (64) 64 (61)
Female 75 (36) 41 (39)
Self-identified Race [N (%)]
White 183 (88) 92 (88)
Asian 10 (5) 5 (5)
Black 8 (4) 4 (4)
Not reported 6 (3) 4 (4)
Age Group [N (%)]
< 65 years 143 (69) 76 (72)
≥ 65 years 64 (31) 29 (28)
Performance Status [N (%)]
0 92 (44) 48 (46)
1 113 (55) 55 (52)
2 2 (1) 2 (2)
Prior Treatment [N (%)]
Surgery (other than biopsy) 194 (94) 98 (93)
Radiotherapy 16 (8) 16 (15)
Imatinib outcome [N (%)]
Intolerance 9 (4) 4 (4)
Progression within 6 months 36 (17) 17 (16)
Progression beyond 6 months 162 (78) 84 (80)
A planned interim efficacy and safety analysis was performed after 149 TTP events had occurred. There was a statistically significant advantage for SUTENT over placebo in the primary endpoint of TTP, as well as in the secondary endpoint of progression-free survival. Data were not mature enough to determine the overall survival benefit. Efficacy results are summarized in Table 5 and the Kaplan-Meyer curve for TTP is in Figure 1.
Table 5. GIST Efficacy Results from Study A (interim analysis) Efficacy Parameter SUTENT
(N = 207) Placebo
(N = 105) P-value (log-rank test) HR
(95% CI)
CI=Confidence interval, HR=Hazard ratio, PR=Partial response
*
Time from randomization to progression; deaths prior to documented progression were censored at time of last radiographic eva luation
†
A comparison is considered statistically significant if the p-value is < 0.0042 (O'Brien Fleming stopping boundary)
‡
Time from randomization to progression or death due to any cause
§
Pearson chi-square test
Time to Tumor Progression*
[median, weeks (95% CI)] 27.3
(16.0, 32.1) 6.4
(4.4, 10.0) <0.0001† 0.33
(0.23, 0.47)
Progression-free Survival‡
[median, weeks (95% CI)] 24.1
(11.1, 28.3) 6.0
(4.4, 9.9) <0.0001† 0.33
(0.24, 0.47)
Objective Response Rate
(PR) [%, (95% CI)] 6.8
(3.7, 11.1) 0 0.006§
Figure 1. Kaplan-Meier Curve of TTP in Study A (Intent-to-Treat Population)
Study B
Study B was an open-label, multi-center, sing
