At the recent 2013 2013 Genitourinary Cancers Symposium there was an abstract presented that updated data from the COU-AA-302 clinical trial of Abiraterone Acetate (Zytiga) with prednisone. The updated data confirms that Zytiga with prednisone improves overall survival (OS) in men with metastatic castrate resistant prostate cancer (mCRPC) post-docetaxel therapy (chemotherapy)(Lancet Oncol 2012;13:983-92).

The trial evaluated 1088 men who were stratified by Eastern Cooperative Oncology Group performance status (ECOG-PS, 0 vs 1) and randomized 1:1 to Zytiga (AA 1000 mg + P 5 mg po BID) vs Placebo + P. In addition to survival the trial also had
co-primary endpoints: radiographic progression-free survival (rPFS) and OS. Median time with 95% CI was estimated using the Kaplan-Meier method. For the statistical anaylisis the O’Brien-Fleming Lan-DeMets ?-spending function was used for OS.

At 55% IA, OS, rPFS and secondary endpoints all favored the AA arm (Table). Median follow-up = 27.1 mos. A post hoc sensitivity multivariate analysis for OS using known prognostic factors supported primary results (HR 0.74, P = 0.0017). Grade 3/4 AEs (AA, P) (%): hypertension 4.2 vs 3.1; hypokalemia 2.6 vs 1.9; ALT? 5.5 vs 0.7; AST? 3.1 vs 0.9.

In updated IA of COU-AA-302, improvement in rPFS (risk reduction 47%) remained statistically significant. However, the risk of death decreased by 21% but did not reach pre-specified efficacy boundary.

Median OS for AA (35.3 mos) is the longest reported for this mCRPC population. Secondary endpoints were clinically and statistically significant. Despite the longer exposure to Zytiga, the safety profile remaind favorable.

Clinical trial information: NCT00887198.

Median Months
AA P HR (95% CI) P value

rPFS 16.5 8.3 0.53 (0.45, 0.62) <0.0001OS* 35.3 30.1 0.79 (0.66, 0.96) 0.0151Time to Opiate Use NR 23.7 0.79 (0.66, 0.96) 0.0002 Time to chemotherapy initiation 26.5 16.8 0.61 (0.51, 0.72) <0.0001 Time to ECOG-PS deterioration 12.3 10.9 0.83 (0.72, 0.94) 0.0052 Time to PSA progression 11.1 5.6 0.50 (0.43, 0.58) <0.0001 Abbreviation: NR, not reached. Clinical cutoff date (CCO): 22 May 2012. *Pre-specified alpha level 0.0035
BOTTOM LINE: On additional analysis, Zytiga was shown to extend overall survival (life) with a tolerable side effect profile.

J Clin Oncol 31, 2013 (suppl 6; abstr 5)
Dana E. Rathkopf, Matthew Raymond Smith, Johann Sebastian De Bono, Christopher Logothetis, Neal D. Shore, Paul L. De Souza, Karim Fizazi, Peter Mulders, Paul N. Mainwaring, John D. Hainsworth, Tomasz M. Beer, Scott A. North, Yves Fradet, Thomas W. Griffin, Youn Choi Park, Thian San Kheoh, Eric Jay Small, Howard I. Scher, Arturo Molina, Charles J. Ryan; Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital Cancer Center, Boston, MA; Institute of Cancer Research/Royal Marsden Hospital, Sutton, United Kingdom; The University of Texas MD Anderson Cancer Center, Houston, TX; Carolina Urologic Research Center, Myrtle Beach, SC; University of Western Sydney School of Medicine, Ingham Institute, Liverpool, Australia; Institut Gustave Roussy, Villejuif, France; Radboud University Medical Centre, Nijmegen, Netherlands; Haematology and Oncology Clinics of Australasia, Brisbane, Australia; Sarah Cannon Research Institute, Nashville, TN; Oregon Health and Science University, Knight Cancer Institute, Portland, OR; Cross Cancer Institute, Edmonton, AB, Canada; Laval University, Québec, QC, Canada; Janssen Research & Development, Los Angeles, CA; Janssen Research & Development, Raritan, NJ; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; University of California, San Francisco, San F

Joel T Nowak. M.A., M.S.W.