PMID- 27160947
OWN - NLM
STAT- MEDLINE
DCOM- 20171226
LR  - 20240326
IS  - 1873-7560 (Electronic)
IS  - 0302-2838 (Print)
IS  - 0302-2838 (Linking)
VI  - 70
IP  - 6
DP  - 2016 Dec
TI  - Phase 2 Study of the Safety and Antitumor Activity of Apalutamide (ARN-509), a 
      Potent Androgen Receptor Antagonist, in the High-risk Nonmetastatic 
      Castration-resistant Prostate Cancer Cohort.
PG  - 963-970
LID - S0302-2838(16)30133-6 [pii]
LID - 10.1016/j.eururo.2016.04.023 [doi]
AB  - BACKGROUND: Apalutamide is a potent androgen receptor (AR) antagonist that 
      targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA 
      binding, and transcription of AR gene targets. OBJECTIVE: To evaluate the 
      activity and safety of apalutamide in patients with high-risk nonmetastatic 
      castration-resistant prostate cancer (nmCRPC). DESIGN, SETTING, AND PARTICIPANTS: 
      We conducted a multicenter phase 2 study of nmCRPC patients with a high risk for 
      progression (prostate-specific antigen [PSA] >/=8 ng/ml or PSA doubling time [PSA 
      DT] </=10 mo). INTERVENTION: Patients received 240mg/d apalutamide while continuing 
      on androgen-deprivation therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 
      Primary end point was 12-wk PSA response (Prostate Cancer Working Group 2 
      criteria). Secondary end points included safety, time to PSA progression (TTPP), 
      and metastasis-free survival (MFS). RESULTS AND LIMITATIONS: A total of 51 
      patients were enrolled; four patients with metastatic disease were excluded from 
      the efficacy analysis. Patient characteristics included median age, 71 yr; 
      Eastern Cooperative Oncology Group performance status 0 (76%); Gleason score </=7 
      (57%); median PSA 10.7 ng/ml; and PSA DT </=10 mo (45%). At median follow-up of 
      28.0 mo, 18 patients (35%) remained in the study. Overall, 89% of patients had 
      >/=50% PSA decline at 12 wk. Median TTPP was 24.0 mo (95% confidence interval [CI], 
      16.3 mo-not reached [NR]); median MFS was NR (95% CI, 33.4 mo-NR). Most of the 
      patients discontinued study treatment (n=33) due to disease progression (n=11 
      [22%]) or adverse events (AEs) (n=9 [18%]). The most common AE was fatigue (any 
      grade, n=31 [61%]) although grade >/=3 fatigue was uncommon (n=2 [4%]). These 
      represent the first apalutamide nmCRPC patient clinical data. CONCLUSIONS: In 
      high-risk nmCRPC patients, apalutamide was safe with robust activity based on 
      durable PSA responses and disease control. PATIENT SUMMARY: Antitumor activity 
      and the safety of apalutamide in patients with nonmetastatic castration-resistant 
      prostate cancer support continued development in this setting. TRIAL 
      REGISTRATION: ClinicalTrials.gov identifier NCT01171898.
CI  - Copyright (c) 2016 European Association of Urology. Published by Elsevier B.V. All 
      rights reserved.
FAU - Smith, Matthew R
AU  - Smith MR
AD  - Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, 
      MA, USA. Electronic address: smith.matthew@mgh.harvard.edu.
FAU - Antonarakis, Emmanuel S
AU  - Antonarakis ES
AD  - Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, 
      MD, USA.
FAU - Ryan, Charles J
AU  - Ryan CJ
AD  - UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
FAU - Berry, William R
AU  - Berry WR
AD  - Cancer Centers of North Carolina, Raleigh, NC, USA.
FAU - Shore, Neal D
AU  - Shore ND
AD  - Carolina Urologic Research Center, Myrtle Beach, SC, USA.
FAU - Liu, Glenn
AU  - Liu G
AD  - University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
FAU - Alumkal, Joshi J
AU  - Alumkal JJ
AD  - Oregon Health & Science University, Knight Cancer Institute, Portland, OR, USA.
FAU - Higano, Celestia S
AU  - Higano CS
AD  - University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA, 
      USA.
FAU - Chow Maneval, Edna
AU  - Chow Maneval E
AD  - Aragon Pharmaceuticals, San Diego, CA, USA.
FAU - Bandekar, Rajesh
AU  - Bandekar R
AD  - Janssen Research & Development, Spring House, PA, USA.
FAU - de Boer, Carla J
AU  - de Boer CJ
AD  - Janssen Biologics, B.V., Leiden, The Netherlands.
FAU - Yu, Margaret K
AU  - Yu MK
AD  - Janssen Research & Development, Los Angeles, CA, USA.
FAU - Rathkopf, Dana E
AU  - Rathkopf DE
AD  - Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New 
      York, NY, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01171898
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20160506
PL  - Switzerland
TA  - Eur Urol
JT  - European urology
JID - 7512719
RN  - 0 (Androgen Receptor Antagonists)
RN  - 0 (Thiohydantoins)
RN  - 0 (apalutamide)
RN  - EC 3.4.21.- (KLK3 protein, human)
RN  - EC 3.4.21.- (Kallikreins)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
SB  - IM
CIN - Eur Urol. 2016 Dec;70(6):971-973. PMID: 27238654
MH  - Aged
MH  - Aged, 80 and over
MH  - Androgen Receptor Antagonists/*therapeutic use
MH  - Disease-Free Survival
MH  - Humans
MH  - Kallikreins/blood
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Prostate-Specific Antigen/blood
MH  - Prostatic Neoplasms, Castration-Resistant/blood/*drug therapy/pathology
MH  - Thiohydantoins/*therapeutic use
MH  - Treatment Outcome
PMC - PMC5568792
MID - NIHMS895646
OTO - NOTNLM
OT  - Antitumor activity
OT  - Apalutamide
OT  - Castration-resistant prostate cancer
OT  - Safety
COIS- Financial disclosures: Matthew R. Smith certifies that all conflicts of interest, 
      including specific financial interests and relationships and affiliations 
      relevant to the subject matter or materials discussed in the manuscript (eg, 
      employment/affiliation, grants or funding, consultancies, honoraria, stock 
      ownership or options, expert testimony, royalties, or patents filed, received, or 
      pending), are the following: Matthew R. Smith has served as a consultant to 
      Janssen Research & Development. Emmanuel S. Antonarakis has served as a 
      consultant/adviser to Janssen Biotech, Astellas, Medivation, ESSA, Sanofi, and 
      Dendreon; he has received research funding from Aragon Pharmaceuticals, Johnson & 
      Johnson, Janssen Biotech, Astellas, Tokai, Sanofi, Dendreon, Exelixis, Novartis, 
      and Genentech. Charles J. Ryan has received honoraria from Janssen Research & 
      Development. William R. Berry has received research grants from AHRQ. Neal D. 
      Shore is a consultant/adviser to Algeta, Amgen, Bayer, BNI, Dendreon, Ferring, 
      Janssen, Millennium, and Sanofi. Glenn Liu has nothing to report. Joshi J. 
      Alumkal has received research funding from Aragon Pharmaceuticals. Celestia S. 
      Higano received consulting fees or honoraria from AbbVie, Algeta, Astellas, 
      Bayer, Dendreon, Genentech, Johnson & Johnson, Medivation, Novartis, Pfizer, and 
      Veridex; grants or research support from Amgen, Aragon Pharmaceuticals, 
      AstraZeneca, Bayer, Dendreon, Exelixis, Genentech, Johnson & Johnson, Medivation, 
      Millennium, Novartis, OncoGenex, Sanofi-Aventis US, Taxynergy, and Teva; and 
      other financial benefits from Cell Therapeutics. Edna Chow Maneval was an 
      employee at Aragon Pharmaceuticals. Rajesh Bandekar is an employee of Janssen 
      Research & Development and holds stock and stock options in Johnson & Johnson. 
      Carla J. de Boer is an employee of Janssen Biologics and holds stock and stock 
      options in Johnson & Johnson. Margaret K. Yu is an employee of Janssen Research & 
      Development and holds stock and stock options in Johnson & Johnson. Dana E. 
      Rathkopf has served as a consultant/adviser to and has received research funding 
      from Janssen Research & Development, AstraZeneca, Celgene, Ferring, Medivation, 
      Millennium/ Takeda, and Novartis.
EDAT- 2016/05/11 06:00
MHDA- 2017/12/27 06:00
PMCR- 2017/08/23
CRDT- 2016/05/11 06:00
PHST- 2016/02/10 00:00 [received]
PHST- 2016/04/21 00:00 [accepted]
PHST- 2016/05/11 06:00 [pubmed]
PHST- 2017/12/27 06:00 [medline]
PHST- 2016/05/11 06:00 [entrez]
PHST- 2017/08/23 00:00 [pmc-release]
AID - S0302-2838(16)30133-6 [pii]
AID - 10.1016/j.eururo.2016.04.023 [doi]
PST - ppublish
SO  - Eur Urol. 2016 Dec;70(6):963-970. doi: 10.1016/j.eururo.2016.04.023. Epub 2016 
      May 6.