Satraplatin AUA 2007 Presentation Notes*
For News of FDA Review

Satraplatin significantly improves Progression Free Survival (PFS) and pain control in patients with advanced hormone-refractory prostate cancer (HRPC): Preliminary results from the phase III SPARC trial

* Notes from slides provided by Oliver Sartor, MD for education of advocates regarding Satraplatin results

SPARC: Randomized 2:1 Double Blind Trial with 950 Enrolled Patients

HRPC: failed 1 prior chemotherapy regimen
Arm A:
     • Satraplatin 80 mg/m2 d1-5 q 35d
     • Antiemetic 1 mg BID d1-5 q 35d
     • Prednisone 5 mg BID
Arm B:
     • Placebo 80 mg/m2 d1-5 q 35d
     • Placebo* 1 mg BID d1-5 q 35d
     • Prednisone 5 mg BID
All patients treated until progression, intolerable toxicity or death. No crossovers allowed

Endpoints

Primary
     • Progression Free Survival (PFS)
     • Overall Survival (OS)
Secondary
     • Time to Pain Progression (TTP)

Eligibility Criteria

• Progressive metastatic HRPC with radiographic or PSA progression after a minimum of 2 courses of one (unspecified) chemotherapy
• Adequate renal, hepatic, and hematologic function
• Performance Status 0-2
• Continuation of prior bisphosphonate therapy was permitted

Definition of PFS
PFS = Composite endpoint based on first occurrence of

• Tumor Progression (RECIST for soft tissue lesions, ? 2 new lesions on bone scan)
• Skeletal Event (fracture, RT, bone surgery, initiation of bisphosphonates)
• Symptomatic Progression (increase in PPI* score or analgesic consumption, worsening of ECOG PS, weight loss >10%)
• Death

Assessment of PFS

• Treatment duration was determined by individual investigators based on their own assessments of PFS and toxicity
• PFS independently assessed by a “blinded” Independent Review Committee (IRC)

Pain Assessment

• Patient diaries (patient reported outcome)
     – Daily Present Pain Intensity (PPI) score
          • McGill-Melzack questionaire
          • 6 point scale: 0 = no pain, 5 = excruciating pain
     – Daily analgesic use
          • For Statistical Analysis, weekly average PPI and analgesic scores were assessed centrally and blindly
     – Analgesic score constructed using normalization of various opioid types and dosing intervals

Pain Progression
• Increase in PPI or analgesic score for = 2 weeks
     – Weekly average PPI
          • = 1 point vs baseline
           or
          • = 2 points vs nadir
     – Weekly average analgesic score
          • > 25% vs baseline

Baseline Patient Characteristics

	Satraplatin n=635	Placebo n=315
Age (Years)
Median	70	68.0
Range	42-88	45-95
Performance Status
0-1	89.8%	89.8%
2	10.2%	10.2%
Pain Index
0	36.8%	33.8%
1-5	63.2%	66.2%
Progression at Entry
Tumor	61.7%	61.9%
PSA only	38.3%	38.1%
Prior chemotherapy
Docetaxel	51.5%	50.8%
Paclitaxel	2.7%	2.9%
Mitoxantrone	20.2%	20.3%
Others	25.6%	26.0%
Bisphosphonate	30.7%	27.3%

Progression Free Survival
ITT Population (# of patients Per Independent Review Committee)

Weeks	0	10	20	30	40	50	60	70	80	90
Satraplatin	635	363	229	143	90	63	43	24	18	12
Placebo	315	140	63	37	24	11	5	5	1

Progression Free Survival
ITT with Prior Docetaxel

Weeks	0	10	20	30	40	50	60	70	80	90
Satraplatin	327	167	107	69	39	28	19	13	9	5
Placebo	160	61	28	16	8	4	1	1

Time to Pain Progression
ITT Population
Satraplatin Placebo

	Satraplatin	Placebo
Pain progression events, N (%)	217 (34.2%)	130 (41.3%)
Median	66.1 weeks	22.3 weeks

Response Rate Analyses

	Satraplatin	Placebo
All Patients
Pain (n = 351/181)	24.2	13.8
PSA (n = 476/225)	25.4	12.4
With Prior Docetaxel
Pain (n = 183/99)	25.7	13.1
PSA (n = 231/109)	28.6	12.8

Hematologic Toxicity
Grade 3/4

	Satraplatin + Prednisone n=635	Placebo + Prednisone n=315
WBC
Grade 3/4	86 (13.7)	2 (0.6)
Grade 4	6 (1.0)	0
Neutrophils
Grade 3/4	133 (21.1)	2 (0.6)
Grade 4	26 (4.1)	0
Febrile neutropenia	2 (0.3%)	0
Platelets
Grade 3/4	133 (21.1)	4 (1.3)
Grade 4	1 (0.2)	0
Platelet transfusions	3.8%	0.3%
Hgb
Grade 3/4	59 (9.4)	10 (3.2)
Grade 4	10 (1.6)	2 (0.6)
RBC transfusions	15.9%	8.0%

Non Hematologic Adverse Events
Grade 3/4

	Satraplatin + Prednisone n=629	Placebo + Prednisone n=313
Bilirubin	0.5%	0.0%
Serum Creatinine	0.8%	0.3%
Nausea	1.3%	0.3%
Vomiting	1.6%	0.0%
Diarrhea	2.1%	0.0%
Constipation	2.1%	1.0%
Fatigue/Asthenia	4.9%	2.6%
Infectious Episodes	4.0%	1.0%
Neuropathy	0.3%	0.3%
DVT	1.6%	0.0%

Summary
     • 33% reduction in risk of disease progression or death
          – Results were consistent across study subsets, including those with prior docetaxel
     • 36% reduction in risk of pain progression
          – Results were consistent across study subsets, including those with prior docetaxel
     • Satraplatin is very well tolerated
          – Grade 4 hematologic events are minimal
           – No grade 3/4 non-hematologic adverse events >5%
     • Satraplatin offers significant clinical benefit in patients currently having an unmet need

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