ARN-509 は米国で臨床研究中の第二世代anti-androgenで、enzalutamide の次にくる薬剤として注目を集めています。
すでに2012年のESMOで転移を有するホルモン不応性前立腺癌（CRPC）、アビラテロン後のCRPCについてはpromising dataが報告されています。
2013ASCOでは転移のないCRPCでの有効性について報告されました。
enzalutamideに比較してけいれんの副作用認められなかったようです。
フェーズ3の報告が待たれます。
ARN-509 in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC).
Subcategory:
Prostate Cancer
Category:
Genitourinary Cancer
Meeting:
2013 Genitourinary Cancers Symposium
Session Type and Session Title:
General Poster Session A: Prostate Cancer
Oral Abstract Session A: Prostate Cancer (eQ&A)
Abstract Number:
07
Citation:
J Clin Oncol 31, 2013 (suppl 6; abstr 7)
Author(s):
Matthew Raymond Smith, Emmanuel S. Antonarakis, Charles J. Ryan, William R. Berry, Neal Shore, Glenn Liu, Joshi J. Alumkal, Celestia S. Higano, Edna Chow Maneval, Dana E. Rathkopf; Massachusetts General Hospital Cancer Center, Boston, MA; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; USCF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; Cancer Centers of North Carolina, US Oncology, Raleigh, NC; Grand Strand Urology, Myrtle Beach, SC; University of Wisconsin Carbone Cancer Center, Madison, WI; Oregon Health and Science University, Knight Cancer Institute, Portland, OR; School of Medicine, University of Washington, Seattle, WA; Aragon Pharmaceuticals, San Diego, CA; Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, NY
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Abstract Disclosures
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-naïve 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 <3 cm below the iliac bifurcation were allowed), and high risk for disease progression based on PSA value ≥ 8 ng/mL within 3 months of enrollment and/or PSA doubling time ≤ 10 months. Patients received ARN-509 at the recommended Phase II dose of 240 mg/day, previously established in Phase I (Rathkopf et al, GU ASCO 2012). The primary endpoint was PSA response rate at 12 weeks according to the Prostate Cancer Working Group 2 Criteria. Secondary endpoints included safety, time to PSA progression and 1-year metastasis-free survival. PSA assessments were collected every 4 weeks and tumor scans were performed every 16 weeks. Results: Forty-seven patients were enrolled between November 2011 and May 2012. The median age was 71 years (range 51 to 88) and at baseline, patients presented with ECOG performance status 0 (77%), Gleason Score 8-10 (32%), and median PSA of 10.7 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 20 weeks, three patients discontinued the study. The most common treatment-related adverse events (AE) were fatigue (30%), diarrhea (28%), nausea (17%), rash (13%), and abdominal pain (11%). The incidence of Grade 3 AEs was 6.4%, and no seizures have been observed to date. The 12-week PSA response was 91% and the time to PSA progression has not been reached. Conclusions: 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. Clinical trial information: NCT01171898.