NDA 21-801 Satraplatin
Proposed Indication
Satraplatin is indicated for the
treatment of patients with androgen
independent (hormone refractory)
prostate cancer who have failed
prior chemotherapy
1
Study Population
• Hormone refractory metastatic prostate
cancer
• Failed one prior chemotherapy regimen
• No prior platinum drug
• ECOG PS 10%)
- Skeletal related events
- Clinical events
- Death
5
Partial Regulatory History
PFS Endpoint
•Oct. 2002-EOP2 - ? Appropriateness of
PFS endpoint.
•May 2003-EOP2 - No agreement on PFS
definition
•June 2005-pre-NDA – No experience with
composite PFS endpoint
•March 2006 - PFS endpoint will be a
review issue
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ODAC Question
•Is the composite PFS endpoint, as
defined, an acceptable endpoint for
treatment evaluation in hormone
refractory prostate cancer?
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Sample Size Considerations
Date Endpoint HR Power # Pts # Events
5/03 OS 1.3 80% 792
7/03 PFS/OS 1.3 85% 912 637 PFS
602 OS
4/04 OS 1.3 85% 912 602 OS
6/05 PFS/OS 1.3 90% 694 PFS
700 OS
2/07 PFS/OS 950 802 PFS
463 (6/06)
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Participant Countries
Country No. Pts Country No. Pts
U.S.A 258 Russia 28
France 141 Croatia 24
Argentina 98 Italy 23
U.K. 85 Peru 23
Poland 71 Hungary 22
Germany 61 Israel 14
Belgium 46 Netherlands 11
Spain 42 Canada 3
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Demographics
Characteristic Total n=950
Age (median (min-max) 70 (42-95) yrs
Race: Caucasian 89%
ECOG 0-1 89%
Current bisphosphonates 30%
PPI = 0 36%
Average analgesic score = 0 41%
Prior docetaxel 51%
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Progression Free Survival
11
Interim Overall Survival
66% Events
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ODAC Question
Should the FDA wait for the final
survival analysis before deciding
whether this application is
approvable?
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PFS Events
Satraplatin Prednisone Total
n=528 n=274 n=802
Radiologic 36% 37% 36%
Pain 35% 43% 37%
Death 9% 5% 8%
PS/Weight 6% 6% 6%
Other 15% 10% 13%
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Radiologic Progression
Independent Radiology Review
• Independent blinded review of all radiology
studies by 2 radiologists
• If the two radiologists disagree as to the
occurrence of progression or response or
if they differ on the date of progression or
response a third radiologist (adjudicator)
reviews the studies and agrees with either
radiologist 1 or radiologist 2
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Adjudicated Radiology Progression
Radiologic No. Number Percent
Adjudicated Adjudicated
Progression 290 116 40%
Not Progression 660 220 33%
Total 950 336 35%
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ODAC Question
As 336 of 950 study patients (35%) required
adjudication to determine progression what
does this indicate about the reliability of
radiologic progression assessment?
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Radiologic Progression
Imaging Methods
Imaging Method Total
N=290
Bone scan only 66%
Bone scan + other 16%
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Radiologic Progression
USA 258
50
France 141
45 Poland 71
40 Peru 23
35 UK 85
Argentina 98
30 Croatia 24
25 Netherlands 11
20 Italy 23
Germany 61
15 Russia 28
10 Israel 14
5 Belgium 46
Spain 42
0
Hungary 22
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Time to Pain Progression
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Pain Progression Assessment
• Based on average weekly Present Pain
Intensity (PPI) and Analgesic Scores (AS)
recorded by patients on pain diaries
• Pain progression
PPI Increase > 1 point from baseline or
> 2 points from nadir observed for > 2
consecutive weeks
• Increase in average AS of >25% (narcotics
only) observed for > 2 consecutive weeks
• Independent blind review
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Baseline PPI
Pain Number of
Score patients (%)
0 (None) 327 (35.9)
1 (Mild) 258 (28.3)
2 (Discomforting) 212 (23.3)
3 (Distressing) 97 (10.6)
4 (Horrible) 14 (1.5)
5 (Excruciating) 3 (0.1)
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Baseline PPI 0, 1 or 2
Narcotic Use
No. %
PPI No. of analgesic analgesic
patients score = 0 score = 0
0 327 301 92
1 258 160 62
2 212 69 33
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Pain and/or Analgesic Progression
USA 258
50
France 141
45 Poland 71
40 Peru 23
UK 85
35 Argentina 98
30 Croatia 24
Netherlands 11
25
Italy 23
20 Germany 61
15 Russia 28
Israel 14
10 Belgium 46
5 Spain 42
Hungary 22
0
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Analgesic Score Progression
% of Pain Progression
USA 258
100
France 141
90 Poland 71
80 Peru 23
70 UK 85
60 Argentina 98
Croatia 24
50
Netherlands 11
40 Italy 23
30 Germany 61
20 Russia 28
10 Israel 14
Belgium 46
0
Spain 42
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ODAC Question
• Was pain progression reliably
assessed in this trial?
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Objective Response Rate
Satraplatin Placebo
N=274* N=134*
CR + PR 8% 0.7%
* Number of patients with soft tissue
lesions
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Drug Exposure
Satraplatin Placebo
+ Pred + Pred
Number of treatment cycles 4 2
Median (range) (1-32) (1-19)
% of patients with
Dose reduction 7 days 44% 11%
Dose increase > 90 mg/m2 8% 10%
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Cycle 1 Hematologic Toxicity
Satraplatin + Pred Placebo + Pred
n=629 n=313
Hemoglobin
All Grades 96% 90%
Grade 3-4 9% 3%
Platelets
All Grades 87% 20%
Grade 3-4 22% 1%
Neutrophils
All Grades 67% 5%
Grade 3-4 21% 1% 29
Grade 3/4 Non-Hematologic TEAEs
Satraplatin + Pred Placebo + Pred
n=629 n=313
Any TEAE 55% 30%
GI Disorders 8% 2%
Infections 5% 1%
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ODAC Discussion Issues
- Is PFS, as defined, an acceptable endpoint for
treatment evaluation in HRPC?
-Was radiologic progression reliably assessed?
-Was pain progression reliably assessed?
-Should FDA should wait for the final survival
analysis before deciding whether this
application is approvable? That analysis
should be available by the end of 2007
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