le-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)].
14.2 Renal Cell Carcinoma
Treatment-Naïve MRCC
A Phase 3 randomized study comparing single-agent SUTENT with IFN-α was conducted in patients with treatment-naïve MRCC. The primary objective was to compare PFS in patients receiving SUTENT versus patients receiving IFN-α. Secondary objectives included TTP, ORR, OS safety and patient reported outcomes (PRO). Seven hundred fifty (750) patients were randomized (1:1) to receive either 50 mg SUTENT once daily on Schedule 4/2 or to receive IFN-α administered subcutaneously at 9 MIU three times a week. Patients are treated until disease progression or withdrawal from the study for another reason.
The ITT population for this interim analysis included 750 patients, 375 randomized to SUTENT and 375 randomized to IFN-α. Baseline age, gender, race and ECOG performance status were comparable and balanced between the SUTENT and IFN-α groups. Demographics and patient characteristics are shown in Table 6. The most common site of metastases present at screening was the lung (78% versus 80%, respectively), followed by the lymph nodes (58% versus 53%, respectively) and bone (30% each arm); the majority of the patients had multiple (2 or more) metastatic sites at baseline (80% versus 77%, respectively).
Table 6. Baseline Demographics in Treatment-Naïve MRCC Study Treatment-Naïve MRCC
SUTENT (n=375) IFN-α (n=375)
*
Patients had ECOG performance status of 1 at screening which changed to 2 at baseline
Gender [n (%)]
Male 267 (71) 269 (72)
Female 108 (29) 106 (28)
Self-identified Race [n (%)]
White 354 (94) 340 (91)
Asian 7 (2) 12 (3)
Black 4 (1) 9 (2)
Not reported 10 (3) 14 (4)
Age Group [n (%)]
< 65 years 223 (59) 252 (67)
≥ 65 years 152 (41) 123 (33)
Performance Status [n (%)]
0 231 (62) 229 (61)
1 144 (38) 142 (38)
2 0 (0) 4 (1)*
Prior Treatment [n (%)]
Nephrectomy 340 (91) 335 (89)
Radiotherapy 53 (14) 54 (14)
A planned interim analysis showed a statistically significant advantage for SUTENT over IFN-α in the primary endpoint of PFS, with PFS for SUTENT more than double that of IFN-α (47.3 and 22.0 weeks, respectively). The secondary endpoint of ORR was more than four times higher for SUTENT than IFN-α (27.5% and 5.3%, respectively). Data were not mature enough to determine the overall survival benefit; at the time of this analysis, 374 of 750 patients enrolled (50%) continued on study, 248/375 (66%) on the SUTENT arm and 126/375 (34%) on the IFN-α arm. Efficacy results are summarized in Table 7 and the Kaplan-Meier curve for PFS is in Figure 2. The results were similar in the supportive analyses and they were robust when controlling for demographic (age, gender, race and performance status) and known risk factors. For 264 of 750 patients (35%) with no MSKCC risk factors,1 media
