IFN-α was conducted in patients with treatment-naïve RCC. The objective was to compare Progression-Free Survival (PFS) in patients receiving SUTENT versus patients receiving IFN-α. Other endpoints included Objective Response Rate (ORR), Overall Survival (OS) and safety. 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 were treated until disease progression or withdrawal from the study.
The ITT population included 750 patients, 375 randomized to SUTENT and 375 randomized to IFN-α. Demographics were comparable between the SUTENT and IFN-α groups with regard to age (59% vs. 67% <65 years for SUTENT vs. IFN-α, respectively), gender (Male: 71% vs. 72%), race (White: 94% vs. 91%, Asian: 2% vs. 3%, Black: 1% vs. 2%, remainder not reported), and Performance Status (ECOG 0: 62% vs. 61%, ECOG 1: 38% each arm, ECOG 2: 0 vs. 1%). Prior treatment included nephrectomy (91% vs. 89%) and radiotherapy (14% each arm). The most common site of metastases present at screening was the lung (78% vs. 80%, respectively), followed by the lymph nodes (58% vs. 53%, respectively) and bone (30% each arm); the majority of the patients had multiple (2 or more) metastatic sites at baseline (80% vs. 77%, respectively).
There was a statistically significant advantage for SUTENT over IFN-α in the endpoint of PFS (see Table 8 and Figure 2). In the pre-specified stratification factors of LDH (>1.5 ULN vs. ≤1.5 ULN), ECOG performance status (0 vs. 1), and prior nephrectomy (yes vs. no), the hazard ratio favored SUTENT over IFN-α. The ORR was higher in the SUTENT arm (see Table 8).
Table 8. Treatment-Naïve RCC Efficacy Results (interim analysis) Efficacy Parameter SUTENT
(n=375) IFN-α
(n=375) P-value (log-rank test) HR
(95% CI)
CI=Confidence interval, NA=Not applicable
Assessed by blinded core radiology laboratory; 90 patients' scans had not been read at time of analysis
A comparison is considered statistically significant if the p-value is < 0.0042 (O'Brien Fleming stopping boundary)
Pearson Chi-square test
Progression-Free Survival* [median, weeks (95% CI)] 47.3
(42.6, 50.7) 22.0
(16.4, 24.0) <0.000001† 0.415
(0.320, 0.539)
Objective Response Rate* [%, (95% CI)] 27.5
(23.0, 32.3) 5.3
(3.3, 8.1) <0.001‡ NA
Figure 2. Kaplan-Meier Curve of PFS in Treatment-Naïve RCC Study (Intent-to-Treat Population)
At the protocol-specified final analysis of OS, the median OS was 114.6 weeks for the SUTENT arm and 94.9 weeks for the IFN-α arm [HR= 0.821, 95% CI (0.673, 1.001)]. The median OS for the IFN-α arm includes 25 patients who discontinued IFN-α treatment because of disease progression and crossed over to treatment with SUTENT as well as 121 patients (32%) on the IFN-α arm who received post-study cancer treatment with SUTENT.
Cytokine-Refractory RCC
The use of single agent SUTENT in the treatment of cytokine-refractory RCC was investigated in two single-arm, multi-center studies. All patients enrolled into these studies experienced failure of prior cytokine-based therapy. In Study 1, failure of prior cytokine therapy was based on radiographic evidence of disease progression defined by RECIST or World Health Organization (WHO) criteria during or within 9 mont |
