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Abiraterone acetate (AA) plus low dose prednisone (P) improves overall survival in patients with metastatic CRPCa who have progressed after docetaxel-based chemotherapy: Results of
COU-AA-301, a randomized placebo controlled phase III study.
Authors: de Bono et al, ESMO, October 2010
Subgroup analysis update: Scher et al, GU ASCO, February 2011
Reviewed by: Dr. Lori Wood
Abstract: ESMO LBA5, GU ASCO Abstract 4
Date posted: May 13, 2011
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Please acknowledge OncologyEducation.ca and Dr. Wood when using these slides.
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BACKGROUND
• After patients with metastatic CRPCa fail docetaxel-based chemotherapy, there were no randomized trials showing a clinically significant benefit to any other agents. In Canada, we often treated patients with mitoxantrone based on phase II data.
• Studies show that CRPCa remains driven by ligand-dependent androgen receptor signaling.
• Abiraterone acetate (AA) is a potent selective inhibitor of CYP17 which is a key enzyme in androgen synthesis.
• Basic science and some clinical data suggest that some CRPCa’s remain dependent on androgen receptor signaling.
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Abiraterone Acetate (AA) 1000 mg po qd +Prednisone 5 mg bidn=797
Placebo +Prednisone 5 mg bidn=398
Metastatic CRPCa
n=1195
Had to HaveReceived Prior Docetaxel Mitoxantrone
1 Outcome = OS
2 Outcomes = PSA Progression,Radiographic Progression, PSA, RR
STUDY DESIGN
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PATIENT CHARACTERISTICS
AA Placebo
Age, Median 69 69
ECOG PS 2 10.7% 11.1%
Significant Pain 44.3% 44.0%
2 Prior Chemotherapy 28.2% 28.4%
Bone Metastases 89.2% 90.4%
Visceral Metastases 29.0% 24.0%
PSA, Median 128.8 137.7
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RESULTS
AA Placebo HR P-value
OS, Median 14.8m 10.9m0.65
(0.54 - 0.77)<0.0001
PSA RR 38% 10% - <0.0001
Radiographic PFS 5.6m 3.6m 0.67 <0.0001
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TOXICITY
AA Placebo
Fluid Retention 30.5% 22.3%
Hypokalemia 17.1% 8.4%
Hypokalemia, grade 3/4 3.8% 0.8%
HTN, grade 3/4 1.3% 0.3%
LFT, abnormal 10.4% 8%
Cardiac 12.5% 9.4%
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SUBGROUP ANALYSIS(GU ASCO 2011)
• All subgroups benefited– ECOG: 0-1 vs. 2– BPI: 4 vs. 4– Prior chemotherapy: 1 vs. 2– Progression: PSA only vs. radiological
PSA– LDH: low vs. high
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STUDY COMMENTARY
• Data reviewed at a pre-specified interim analysis and IDMC recommended study be unblinded.
• AA shows a 3.8m survival advantage over placebo post docetaxel-based chemotherapy in patients with metastatic CRPCa.
• Very well-tolerated.
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BOTTOM-LINE FOR CANADIAN MEDICAL ONCOLOGISTS
• This study will change practice.• Results from another post docetaxel phase III
trial (TROPIC: Cabazitaxel vs. Mitoxantrone) were reported at ASCO 2010. Median OS 15.1m vs. 12.7m
• Given the ease of administration and low toxicity, AA will likely become the standard of care post docetaxel-based chemotherapy in men with metastatic CRPCa.