TENT were permitted to continue treatment per investigator judgment.
At the time of a pre-specified interim analysis, the intent-to-treat (ITT) population included 312 patients. Two-hundred seven (207) patients were randomized to the SUTENT arm, and 105 patients were randomized to the placebo arm. Demographics were comparable between the SUTENT and placebo groups with regard to age (69% vs 72% <65 years for SUTENT vs. placebo, respectively), gender (Male: 64% vs. 61%), race (White: (88% both arms, Asian: 5% both arms, Black: 4% both arms, remainder not reported), and Performance Status (ECOG 0: 44% vs. 46%, ECOG 1: 55% vs. 52%, and ECOG 2: 1 vs. 2%). Prior treatment included surgery (94% vs. 93%) and radiotherapy (8% vs. 15%). Outcome of prior imatinib treatment was also comparable between arms with intolerance (4% vs. 4%), progression within 6 months of starting treatment (17% vs. 16%), or progression beyond 6 months (78% vs. 80%) balanced.
The 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 TTP, meeting the primary endpoint. Efficacy results are summarized in Table 7 and the Kaplan-Meier curve for TTP is in Figure 1.
Table 7. GIST Efficacy Results from Study A (Double-Blind Treatment Phase) 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 < 0.00417 (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 GIST Study A (Intent-to-Treat Population)
The final ITT population enrolled in the double-blind treatment phase of the study included 243 patients randomized to the SUTENT arm and 118 patients randomized to the placebo arm. After the primary endpoint was met at the interim analysis, the study was unblinded, and patients on the placebo arm were offered open-label SUTENT treatment. Ninety-nine of the patients initially randomized to placebo crossed over to receive SUTENT in the open-label treatment phase. At the protocol specified final analysis of OS, the median OS was 72.7 weeks for the SUTENT arm and 64.9 weeks for the placebo arm [HR= 0.876, 95% CI (0.679, 1.129)].
Study B
Study B was an open-label, multi-center, single-arm, dose-escalation study conducted in patients with GIST following progression on or intolerance to imatinib. Following identification of the recommended Phase 2 regimen (50 mg once daily on Schedule 4/2), 55 patients in this study received the 50 mg dose of SUTENT on treatment Schedule 4/2. Partial responses were observed in 5 of 55 patients [9.1% PR rate, 95% CI (3.0, 20.0)].
14.2Renal Cell Carcinoma
Treatment-Naïve RCC
A multi-center, international randomized study comparing single-agent SUTENT with |
