Abstract CT239: ARN-509 in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with abiraterone acetate (AA)
Authors: Rathkopf Dana E. , Antonarakis Emmanuel S. , Shore Neal D. , Tutrone Ronald , Alumkal Joshi J. , Ryan Charles J. , Saleh Mansoor N. , Hauke Ralph J. , Bandekar Rajesh , Maneval Edna Chow , Boer Carla de , Todd Mary , Yu Margaret K. , Scher Howard I. 
Published: May 2015

Abstract
Background:
ARN-509 is a novel second-generation antiandrogen that binds directly to the ligand-binding domain of the androgen receptor (AR), impairing AR nuclear translocation and DNA binding to the androgen response element. Phase 2 of a multicenter phase 1/2 study evaluates ARN-509 activity in 3 distinct patient populations of men with CRPC: 1) nonmetastatic chemotherapy-naive CRPC; 2) chemotherapy-naïve mCRPC; 3) mCRPC post-AA treatment. Study ARN-509-001 is the first to prospectively examine response to novel second-generation antiandrogens post-AA treatment. We present the results of the post-AA treated cohort, as of July 2013.
Methods:
All patients had mCRPC with progressive disease based on rising prostate-specific antigen (PSA) and/or imaging. No prior chemotherapy for CRPC was allowed. Patients in the AA-pretreated cohort had to have been treated with AA for at least 6 months. All patients received ARN-509 at the recommended phase 2 dose of 240 mg/d (Rathkopf et al. J Clin Oncol. 2013). The primary end point was PSA response at 12 weeks according to the Prostate Cancer Working Group 2 criteria. Secondary end points included safety, time to PSA progression, and objective response rates. PSA assessments were collected every 4 weeks and tumor imaging was performed every 12 weeks.
Results:
By July 2013, 21 patients were enrolled and treated in the post-AA cohort. The median age was 67 years (range 48-83). At baseline, 62% of patients had an Eastern Cooperative Oncology Group performance status 0, and 29% had a Gleason score ≥ 8; median PSA was 58.4 ng/mL. Median duration on ARN-509 treatment post AA was 5.6 months (range 1.9-16.7). At 12 weeks, 24% (5/21) of patients had ≥ 50% decline in PSA from baseline. Median time to PSA progression was 16 weeks (95% confidence interval, 12-31 weeks). The best objective response was stable disease in 4 (36%) patients. Patients discontinued the study due to disease progression (n = 13), adverse events (n = 2), consent withdrawn (n = 1), and other reasons (n = 4). The most common treatment-related adverse events were fatigue (n = 11), nausea (n = 5), and diarrhea (n = 3).
Conclusions:
In men with mCRPC, post-AA treatment, ARN-509 is safe and well tolerated, with modest activity in a subset of patients who develop resistance to AA. Clinical trial information: NCT01171898.
Citation Format: Dana E. Rathkopf, Emmanuel S. Antonarakis, Neal D. Shore, Ronald Tutrone, Joshi J. Alumkal, Charles J. Ryan, Mansoor N. Saleh, Ralph J. Hauke, Rajesh Bandekar, Edna Chow Maneval, Carla de Boer, Mary Todd, Margaret K. Yu, Howard I. Scher. ARN-509 in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with abiraterone acetate (AA). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT239. doi:10.1158/1538-7445.AM2014-CT239