761PD - Novel antiandrogen ARN-509 in high-risk non-metastatic (M0) castration-resistant prostate cancer (CRPC)

Date 28 September 2014
Event ESMO 2014
Session Genitourinary tumours, prostate
Topics Clinical Research
Prostate Cancer
Basic Scientific Principles
Presenter Matthew Smith
Citation Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336
Authors M.R. Smith1, E.S. Antonarakis2, C.J. Ryan3, W. Berry4, N.D. Shore5, G. Liu6, J. Alumkal7, C. Higano8, E. Chow-Maneval9, R. Bandekar10, C. De Boer11, M. Todd12, M. Yu13, D.E. Rathkopf14
  • 1Hematology-oncology, Harvard Medical School and Massachusetts General Hospital Cancer Center, 02114 - Boston/US
  • 2Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore/US
  • 3Department Of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, 94115 - San Francisco/US
  • 4Oncology, Cancer Centers of North Carolina, Raleigh/US
  • 5Urology, Carolina Urologic Research Center, Myrtle Beach/US
  • 6Oncology, University of Wisconsin Carbone Cancer Center, 53792 - Madison/US
  • 7Medicine, Oregon Health & Science University, Knight Cancer Institute, Portland/US
  • 8Department Of Medicine, University of Washington, Fred Hutchinson Cancer Research Center, 98109 - Seattle/US
  • 9Clinical Research, Seragon Pharmaceuticals, San Diego/US
  • 10Biostats Oncology, Janssen Research & Development, Philadelphia/US
  • 11Oncology, Janssen Biologics, B. V., Leiden/NL
  • 12Oncology, Janssen Global Services, Raritan/US
  • 13Wc Clinical Oncology, Janssen Research & Development, Los Angeles/US
  • 14Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York/US

Abstract

Aim

ARN-509 selectively binds the androgen receptor and impairs its nuclear translocation and DNA binding to androgen response elements. Study ARN-509-001 evaluates ARN-509 activity in pts with high-risk M0 CRPC, chemotherapy-naïve metastatic CRPC (mCRPC), and mCRPC post abiraterone acetate. We report the updated results for the M0 CRPC cohort as of February 2014.

Methods

All pts had CRPC with no radiographic evidence of metastases (pelvic lymph nodes < 3 cm below the iliac bifurcation were allowed) and high risk for disease progression based on prostate-specific antigen (PSA) ≥ 8 ng/mL within 3 mos of enrollment and/or PSA doubling time (PSADT) ≤ 10 mos. All pts received ARN-509 240 mg/d. Primary end point: PSA response at 12 weeks according to Prostate Cancer Working Group 2 (PCWG2) criteria. Secondary end points: safety, time to PSA progression, and metastasis-free survival (MFS). PSA was measured every 4 wks and tumor imaging was performed every 16 wks.

Results

M0 CRPC cohort enrolled 51 pts from Nov 2011 to Jun 2012; 4 pts had metastatic disease and were excluded from the efficacy analysis. Median age was 71 years (range 51–88). Baseline characteristics were: ECOG performance status, 0 (76%); Gleason score, ≤ 7 (57%); median PSA, 10.7 ng/mL (range 0.5-201.7); and PSADT, ≤ 10 mos (45%). All pts received prior treatment with a luteinizing hormone–releasing hormone analog with or without a first-generation antiandrogen. At median follow-up of 20.2 mos, 29 (57%) pts remain on study. Pts discontinued due to disease progression (n = 7), adverse events (AEs) (n = 7), or other reasons (n = 8). Most common treatment-emergent AEs: fatigue (57%), diarrhea (41%), nausea (29%), dysgeusia (20%), arthralgia (18%), and weight decreased (16%). No seizures were reported.

Efficacy M0 CRPC
N 47
PSA responsea,b, n (%)
12 wks 42/46 (91)
24 wks 40/46 (87)
36 wks 22/46 (48)
Median time to PSA progression, wks (95% CI) NR (67, NR)
Median MFS, wks (95% CI) NR (NR, NR)

NR, not reached. a≥ 50% decline in PSA from baseline per PCWG2. b1 pt did not have postbaseline PSA results.

Conclusions

ARN-509 is well tolerated in pts with high-risk M0 CRPC with robust activity based on durable PSA responses and disease control.

Disclosure

M.R. Smith: has served as a consultant/advisor to and received research funding from Janssen; E.S. Antonarakis: has received honoraria and research funding from Janssen; C.J. Ryan: has received honoraria from Janssen;W. Berry: has served on a speaker bureau for Janssen;N.D. Shore: has served as a consultant/advisor to Astellas, Algeta, Bayer, Ferring, Dendreon, Janssen, Millennium, Sanofi, and BNIT;G. Liu: has received research funding from Aragon and Janssen;C. Higano: has served as a consultant/advisor to Astellas/Medivation, Bayer, Dendreon, and Johnson & Johnson, and has received research funding from Algeta, Aragon, Astellas/Medivation, Dendreon, and Sanofi;R. Bandekar, C. De Boer, M. Todd and M. Yu: is an employee of Janssen and holds stock in Johnson & Johnson;D.E. Rathkopf: has served as a consultant/advisor for Johnson & Johnson and has received research funding (uncompensated) from Celgene, Janssen/J&J, Medivation/Astellas, Millennium, and Novartis. All other authors have declared no conflicts of interest.