ARN-509 in Men with High Risk Non-Metastatic Castration-Resistant Prostate Cancer

ABSTRACT Background ARN-509 is a novel second-generation anti-androgen that binds directly to the ligand-binding domain of the androgen receptor, impairing nuclear translocation and DNA binding. The Phase II portion of a multicenter Phase I/II study is evaluating the activity of ARN-509 in 3 distinct patient populations of men with CRPC (high risk non-metastatic CRPC, metastatic treatment-naive CRPC, and progressive disease after abiraterone acetate). Preliminary results for the cohort of patients with high-risk non-metastatic CRPC are presented here. Methods All patients had CRPC, no radiographic evidence of metastases (pelvic lymph nodes Results Fifty patients were enrolled between November 2011 and May 2012. The median age was 72 years (range 51 to 86) and at baseline, patients presented with ECOG performance status 0 (67%), Gleason Score 8-10 (38%), and median PSA of 11.5 ng/mL. All patients received prior treatment with a LHRH analog with or without a first-generation anti-androgen. At a median treatment duration of 8 weeks, only one patient discontinued the study (due to inability to comply with the protocol). The most common adverse events (AE) were fatigue (13%), diarrhea (9%), nausea (6%) and abdominal pain (6%). There were no Grade > 2 AEs and no patients required dose modifications. At 12 weeks, 17/19 patients (89.5%) of patients had a PSA response. The median decrease in PSA from baseline to week 12 was 83.3%. Conclusion In men with high-risk non-metastatic CRPC, ARN-509 is safe and well tolerated with promising preliminary activity based on high PSA response rates. Disclosure E. Chow-Maneval: As an employee of Aragon Pharmaceuticals, I have stock ownership in Aragon Pharmaceuticals.All other authors have declared no conflicts of interest.