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• The study was designed to have 80% power at a 1-sided significance level of 5% (risk alpha)
• Non-inferiority margin of HR: upper 95% CI ≤1.20 for sunitinib alone
• Enrolment of 576 patients needed to observe 456 events for demonstration of non-inferiority
• Two interim analyses were planned (after 152 and 302 events)
• Monitored by independent DSMB
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CI, confidence interval; HR, hazard ratio
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Study conduct
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• From Sept. 2009 to Sept. 2017, 450 patients were enrolled
• Second interim analysis, cutoff Sept. 9, 2017: 326 events had
occurred
• Median follow-up 50.9 months
• Based on overall survival results, the Steering Committee
decided to stop the trial and considered this interim analysis
as final
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Patient disposition
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ITT, intention to treat Data cutoff : September 9, 2017
450 patients
randomized
Arm B: Sunitinib alone
(n=224) 8 inclusion criteria deviation
Arm A: Nephrectomy + sunitinib
(n=226) 6 inclusion criteria deviation
Safety population
Arm B: Sunitinib alone (213)
38 received secondary
nephrectomy, including 3 not
treated with sunitinib
161 deaths
2 lost to follow up
Safety population
Arm A: Nephrectomy + sunitinib (186)
3 withdrawal of consent
16 not operated
165 deaths
2 lost to follow up
40 did not receive sunitinib 11 did not receive sunitinib
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Patient population
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ITT, intention to treat Data cutoff : September 9, 2017
Arm B: (n=224) Arm A: (n=226)
Sunitinib (n=206)
Nephrectomy (n=205)
ITT population
Nephrectomy + sunitinib (n=176)
450 patients
randomized
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Patient population
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PP1, per protocol Data cutoff : September 9, 2017
Arm B: (n=224) Arm A: (n=226)
Sunitinib (n=206)
Nephrectomy (n=205)
PP1 population
Nephrectomy + sunitinib (n=176)
450 patients
randomized
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Patient population
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PP2 : per protocol Data cutoff : September 9, 2017
Arm B: (n=224) Arm A: (n=226)
Sunitinib (n=206)
Nephrectomy (n=205)
PP2 population
Nephrectomy + sunitinib (n=176)
450 patients
randomized
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Patient characteristics (1)
Characteristic
Arm A:
Nephrectomy + sunitinib
(N = 226)
Arm B:
Sunitinib alone
(N = 224)
Median age (range), years 63 (33–84) 62 (30–87)
Male sex, n (%) 169 (75) 167 (75)
MSKCC score, n (%)
Intermediate 125 (56) 131 (59)
Poor 100 (44) 93 (41)
Missing 1 0
ECOG PS, n (%)
0 130 (57) 122 (54)
1 96 (42) 102 (45)
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CN, cytoreductive nephrectomy; ECOG PS, Eastern Cooperative Oncology Group performance status; MSKCC, Memorial Sloan Kettering Cancer Center
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Characteristic
Arm A:
Nephrectomy + sunitinib
(N = 226)
Arm B:
Sunitinib alone
(N = 224)
Median size of primary tumor, mm
(range) 88 (6–200) 86 (12–190)
Median number of metastatic sites, n
(range) 2 (1–5) 2 (1–5)
Tumor burden* by RECIST v1.1, mm
(range) 140 (23–399) 144 (39–313)
Location of metastases, n (%)
Lung 172 (79) 161 (73)
Bone 78 (36) 82 (37)
Lymph nodes 76 (35) 86 (39)
Other 78 (36) 90 (40)
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*Assessed as a combination of primary renal tumour and metastases.
RECIST, Response Evaluation Criteria In Solid Tumors
Patient characteristics (2)
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Overall survival (ITT)
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Nephrectomy + sunitinib
Sunitinib alone
Median follow-up was 50.9 months (range 0.0–86.6)
HR 95%CI = 0.89 (0.71–1.10)
Non inferiority study ≤1.20
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Overall survival (ITT)
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Non inferiority study ≤1.20
Median OS, months
(95% CI)
Arm A:
Nephrectomy + Sunitinib
(n = 226)
Arm B:
Sunitinib alone
(n = 224)
HR
(95% CI)
Overall 13.9
(11.8–18.3)
18.4
(14.7–23.0)
0.89
(0.71–1.10)
MSKCC intermediate risk 19.0
(12.0–28.0)
23.4
(17.0–32.0)
0.92
(0.6–1.24)
MSKCC poor risk 10.2
(9.0–14.0)
13.3
(9.0–17.0)
0.86
(0.62–1.17)
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Overall survival by patient population
Population Arm A
(Nephrectomy + sunitinib)
Arm B
(Sunitinib) HR (95% CI),
stratified by
MSKCC risk
group n Events, n (%)
Median
(95% CI),
months
n Events, n (%)
Median
(95% CI),
months
ITT 226 165 (73) 13.9
(11.8–18.3) 224 161 (72)
18.4
(14.7–23.0)
0.89
(0.71–1.10)
PP1* 205 149 (73) 14.5
(11.9–20.2) 206 143 (69)
20.5
(15.6–25.2)
0.87
(0.69–1.1)
PP2# 176 122 (64) 18.3
(13.7–23.2) 206 143 (69)
20.5
(15.6–25.2)
0.98
(0.77–1.25)
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*The PP1 analysis included only patients who had nephrectomy in Arm A, and patients who receive sunitinib in Arm B.
#The PP2 analysis included only patients who had nephrectomy and receive sunitinib after nephrectomy in Arm A, and patients who receive sunitinib in Arm B.
CI, confidence interval; HR, hazard ratio; ITT, intent-to-treat; MSKCC, Memorial Sloan Kettering Cancer Center; PP, per-protocol.
Population Arm A: Nephrectomy + sunitinib Arm B: Sunitinib alone HR (95% CI),
stratified by
MSKCC risk
group n Events, n (%) Median (95% CI),
months n Events, n (%)
Median (95%
CI), months
ITT 226 194 (86) 7.2
(6.7–8.5) 224 196 (87)
8.3
(6.2–9.9) 0.82 (0.67-1.00)
PP1* 205 178 (87) 7.6
(6.8–9.4) 206 181 (88)
8.5
(7.5–10.2) 0.82 (0.66-1.01)
PP2# 176 154 (87) 8.7
(7.2–10.2) 206 181 (88)
8.5
(7.5–10.2) 0.87 (0.70-1.08)
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*The PP1 analysis included only patients who had nephrectomy in Arm A, and patients who receive sunitinib in Arm B.
#The PP2 analysis included only patients who had nephrectomy and receive sunitinib after nephrectomy in Arm A, and patients who receive sunitinib in Arm B.
CI, confidence interval; HR, hazard ratio; ITT, intent-to-treat; MSKCC, Memorial Sloan Kettering Cancer Center; PP, per-protocol.
Progression free survival by patient population
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Response rate
Best overall response, n (%) Arm A: Nephrectomy + sunitinib