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4553 Background: AA, a potent oral CYP17A1 inhibitor is approved for treatment of mCRPC with a survival advantage of 4.9 months. In clinical practice, response evaluation remains challenging for pts with mCRPC. CTC conversion from CTC ≥ 5 to CTC < 5 with treatment predicts for improved overall survival in mCRPC. We hypothesized that pts continue to have durable disease stability beyond PSA progression on AA. Methods: Prostate Specific Antigen (PSA) responses, radiological responses and CTC conversion rates were retrospectively analysed in pts treated on AA at our institution. CTCs, PSA and imaging were obtained at predefined time points during these studies. Radiological and PSA progression were defined by standard Prostate Cancer Working Group Criteria II. Clinical progression consisted of worsening disease related pain, skeletal events or declining performance status.Pearson’s chi-squared test and the Kaplan-Meier method were used for this analysis. Results: 141 patients [ECOG Performance Status 0-2; Median Age: 69.7 (range 44.7-87.1); 85 post-docetaxel, 56 pre-docetaxel] received AA. The median duration of clinical and radiological stable disease (SD) was 16.8 months (n=55) and 5.6 months (n=75) in patients with a baseline CTCs count of ≤ 5 cells/7.5mls and ≥ 5 cells/7.5 mls respectively. In the 105 patients with documented PSA progression on AA there was a median 5.7-month delay in detecting radiological and/or clinical progression (95% CI: 4.2, 8.4; range 0.3, 35.6 months). Radiological and clinical SD of ≥ 1 year, ≥ 2 years and ≥ 3 years on AA was observed in 43/141 (30.5%), 21/141 (14.9%) and 12/141 (8.5%) respectively. Conclusions: Radiological and clinical disease stabilization beyond PSA progression is maintained in a high proportion of mCRPC patients treated with AA. Future studies should evaluate whether continued AA treatment beyond PSA and radiological progression can impact outcome.

Background: AA, a potent oral irreversible inhibitor of CYP17A1, has been recently approved for patients with CRPC progressing after docetaxel. CTC count ≥ 5/7.5 ml correlates with worse survival in CRPC. In this analysis we evaluated PSA responses, radiological responses and CTC conversion rates in relation to patient outcome. Methods: 141 patients (ECOG Performance Status 0-2; Median Age: 69.7; 85 post-docetaxel, 56 pre-docetaxel) treated with AA at the Royal Marsden NHS Foundation Trusts between December 2005 and March 2011 were included in this retrospective analyses. CTCs were enumerated using CellSearch at screening, baseline, at multiple time points during the study and at treatment discontinuation. PSA and imaging (Computer Tomography and Bone Scans) were obtained at the same time points as CTC collection. The Kaplan-Meier method was utilized for these analyses. Results: Baseline CTCs of ≥ 5 cells/7.5 ml were detectable in 17/53 (32.1%) pre-docetaxel patients (3 inevaluable) and 58/77 (75.3%) post-docetaxel patients (8 inevaluable at baseline). CTC conversion (≥ 5 to < 5 cells/7.5 ml) was observed in 10/17 (58.8%) pre-docetaxel patients and in 12/52 (23.1%) (6 inevaluable) post-docetaxel patients. PSA responses by PCWG II were observed in 16/22 (72.7%) of patients who attained a CTC conversion. PSA responses were seen in 8/47 (17.0%) patients in the absence of a corresponding CTC conversion. The median duration of radiological SD was 12.13 months (n=55) and 5.4 months (n=75) in patients with a baseline CTCs count of ≤ 5 cells/7.5mls and ≥ 5 cells/7.5 mls respectively. Overall, radiological stable disease was observed for a median of 6 months (95% CI: 4.2, 8.4; range 0.3, 35.6) beyond PSA progression in the 105 patients who experienced PSA progression. Radiological and clinical disease stability during treatment of ≥ 1 year, ≥ 2 years and ≥ 3 years was observed in 43/141 (30.5%), 21/141 (14.9%) and 12/141 (8.5%) respectively. Conclusion: Radiological and clinical disease stabilization beyond PSA progression is seen in a significant proportion of patients treated with AA. CTCs conversion correlates with PSA response and radiological disease stability. Citation Format: Diletta Bianchini, Alison Reid, Gerhardt Attard, Johann De Bono, Shahneen Sandhu, Amy Cassidy Mulick, Deborah Mukherji, Carmel Pezaro, Andrea Zivi, Aurelius Omlin, Ajit Sarvadikar, Emilda Thompson. Treatment response to abiraterone acetate (AA) in patients with castration-resistant prostate cancer (CRPC) based on circulating tumor cells (CTCs), prostate-specific antigen (PSA), and imaging [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C9.