1. www.OncologyEducation.ca 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

2. www.OncologyEducation.ca Thank you for downloading this update. Please feel free to use it for educational purposes. Please acknowledge OncologyEducation.ca and Dr. Wood when using these slides.

3. www.OncologyEducation.ca 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.

4. www.OncologyEducation.ca Abiraterone Acetate (AA) 1000 mg po qd + Prednisone 5 mg bid n=797 Placebo + Prednisone 5 mg bid n=398 Metastatic CRPCa n=1195 Had to Have Received Prior Docetaxel  Mitoxantrone  1 Outcome = OS  2 Outcomes = PSA Progression, Radiographic Progression, PSA, RR STUDY DESIGN

5. www.OncologyEducation.ca PATIENT CHARACTERISTICS AAPlacebo Age, Median69 ECOG PS 210.7%11.1% Significant Pain44.3%44.0% 2 Prior Chemotherapy28.2%28.4% Bone Metastases89.2%90.4% Visceral Metastases29.0%24.0% PSA, Median128.8137.7

6. www.OncologyEducation.ca RESULTS AAPlaceboHRP-value OS, Median14.8m10.9m 0.65 (0.54 - 0.77) <0.0001 PSA RR38%10%-<0.0001 Radiographic PFS5.6m3.6m0.67<0.0001

7. www.OncologyEducation.ca TOXICITY AAPlacebo Fluid Retention30.5%22.3% Hypokalemia17.1%8.4% Hypokalemia, grade 3/43.8%0.8% HTN, grade 3/41.3%0.3% LFT, abnormal10.4%8% Cardiac12.5%9.4%

8. www.OncologyEducation.ca 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

9. www.OncologyEducation.ca 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.

10. www.OncologyEducation.ca 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.