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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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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.