864 Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate (AA) therapy in patients with metastatic castration-resistant prostate cancer (mCRPC)? An analysis of AA phase 3 trials Eur Urol Suppl 2014;13;e864 Print! Print! Stöckle M. 1 , Flaig T.2 , Ohlmann C.H.3 , Scher H.I.4 , De Bono J.S.5 , Rathkopf D.4 , Ryan C.J. 6 , Kheoh T.7 , Li J. 8 , Todd M. 9 , Griffin T.W. 10 , Molina A. 11 , Fizazi K. 12 1 Saarland University, Dept. of Urology and Children Urology, Homburg/Saar, Germany, 2 University of Colorado Cancer Center, University of Colorado School of Medicine, Dept. of Oncology, Aurora, United States of America, 3 Saarland University, Dept. of Urology, Homburg/Saar, Germany, 4 Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, Dept. of Genitourinary Oncology Service, New York, United States of America, 5 The Institute of Cancer Research and The Royal Marsden Hospital, Dept. of Drug Development, Sutton, United Kingdom, 6 Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, Dept. of Medicine, San Francisco, United States of America, 7 Janssen Research & Development, Dept. of Biostatistics & Programming, Los Angeles, United States of America, 8 Janssen Research & Development, Dept. of Biostatistics Oncology, Raritan, United States of America, 9 Janssen Global Services, Dept. of Oncology, Raritan, United States of America, 10 Janssen Research & Development, Dept. Clinical Oncology, Los Angeles, United States of America, 11 Janssen Research & Development, Dept. of Oncology Scientific Innovation, Menlo Park, United States of America, 12 Institut Gustave Roussy, University of Paris Sud, Dept. of Uro-Genitologie, Villejuif, United States of America INTRODUCTION & OBJECTIVES: Gleason score (GS) is strongly prognostic in localized prostate cancer, but less so in mCRPC. 1,2 Patients with high-risk localized prostate cancer and high GS who undergo radiation therapy benefit from long-term androgen deprivation therapy. 3 The impact of GS at initial diagnosis on response to AA therapy in patients with mCRPC is unknown. We retrospectively evaluated efficacy outcomes in patients with mCRPC treated with AA plus prednisone (P) vs P alone in pivotal studies COU-AA-301 (postdocetaxel) and COU-AA-302 (chemo-naïve) by GS at initial diagnosis(≥ 8 or < 8). MATERIAL & METHODS: 1048 patients in COU-AA-301 and 996 in COU-AA-302 with mCRPC treated with AA 1 g + P 5 mg po BID or placebo + P had GS data at diagnosis. Efficacy end points evaluated: overall survival (OS), radiographic progression free survival (rPFS), and time to prostate-specific antigen progression (TTPP).4-6 Distributions and medians were estimated by the Kaplan-Meier method, and hazard ratio (HR) and 95% confidence interval were estimated by the Cox model. RESULTS: Proportion of patients with GS ≥ 8 and GS < 8 was similar across treatment groups and studies. Outcomes by GS are summarized in Table. GS < 8 GS ≥ 8 Median, mos HR (95% CI) p Value Median, mos HR (95% CI) p Value AA + P P AA + P P 356 mCRPC post-docetaxel n 342 161 189 OS 16.3 13.4 0.82 (0.64-1.04) 0.1041 15.5 10.3 0.61 (0.49-0.76) <0.0001 rPFS 6.4 5.5 0.70 (0.56-0.86) 0.0009 5.6 2.9 0.58 (0.48-0.72) <0.0001 TTPP 8.6 8.5 0.78 (0.56-1.08) 0.1346 8.4 5.6 0.47 (0.33-0.65) <0.0001 mCRPC chemo-naïve n 225 254 263 254 OS NRa 31.0 0.72 (0.54-0.97) 0.0295 31.6 30.0 0.84 (0.64-1.09) 0.1786 rPFS 16.5 8.2 0.44 (0.35-0.56) <0.0001 13.8 8.2 0.61 (0.48-0.77) <0.0001 TTPP 11.1 5.6 0.53 (0.42-0.66) <0.0001 11.0 5.6 0.47 (0.38-0.59) <0.0001 a NR, not reached; >34 mos. CONCLUSIONS: The benefit of AA + P vs P alone in post-docetaxel and chemo-naïve patients with mCRPC was independent of GS (≥ 8 or < 8) at initial diagnosis. In this era of novel androgen signalling targeted agents, GS at initial diagnosis may not be relevant in predicting efficacy with AA for patients with mCRPC. 1 Halabi S, J Clin Oncol 2003; 2 Armstrong AJ, Eur J Cancer 2010; 3 Horwitz EM, J Clin Oncol 2008; 4 de Bono JS, NEJM 2011; 5 Fizazi K, Lancet Oncol 2012; 6 Ryan CR, NEJM 2013.
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