ARN-509 in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC).

• DOI: 10.1200/jco.2013.31.6_suppl.7
• Publication Date: 2017-02-24T11:05:51Z
• Authors: Matthew Raymond S...; Emmanuel S. Anton...; Charles J. Ryan; William R. Berry; Neal Shore; Glenn Liu; Joshi J. Alumkal; Celestia S. Higano; Edna Chow Maneval; Dana E. Rathkopf
• Keywords: Clinical endpoint; Abiraterone acetate

7 Background: ARN-509 is a novel second-generation anti-androgen that binds directly to the ligand-binding domain of androgen receptor, impairing nuclear translocation and DNA binding. The Phase II portion multicenter I/II study evaluating activity in 3 distinct patient populations men with CRPC (high risk non-metastatic CRPC, metastatic treatment-naïve progressive disease after abiraterone acetate). Preliminary results for cohort patients high-risk are presented here. Methods: All had no radiographic evidence metastases (pelvic lymph nodes <3 cm below iliac bifurcation were allowed), high progression based on PSA value ≥ 8 ng/mL within months enrollment and/or doubling time ≤ 10 months. Patients received at recommended dose 240 mg/day, previously established I (Rathkopf et al, GU ASCO 2012). primary endpoint was response rate 12 weeks according Prostate Cancer Working Group 2 Criteria. Secondary endpoints included safety, 1-year metastasis-free survival. assessments collected every 4 tumor scans performed 16 weeks. Results: Forty-seven enrolled between November 2011 May 2012. median age 71 years (range 51 88) baseline, ECOG performance status 0 (77%), Gleason Score 8-10 (32%), 10.7 ng/mL. prior treatment LHRH analog or without first-generation anti-androgen. At duration 20 weeks, three discontinued study. most common treatment-related adverse events (AE) fatigue (30%), diarrhea (28%), nausea (17%), rash (13%), abdominal pain (11%). incidence Grade AEs 6.4%, seizures have been observed date. 12-week 91% has not reached. Conclusions: In safe well tolerated promising preliminary rates. Clinical trial information: NCT01171898.