Evidence map›Paper›PMID 27160947›Full record

Trial reportEuropean urology2016

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.

Matthew R Smith, Emmanuel S Antonarakis, Charles J Ryan, William R Berry, Neal D Shore, Glenn Liu, Joshi J Alumkal, Celestia S Higano, Edna Chow Maneval, Rajesh Bandekar and 3 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European urology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01171898 (An Open-Label, Phase 1/2, Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 in Patients With Progressive Advanced Castration-Resistant Prostate Cancer), which is not on this map. Cited by 58 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
15.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01171898 phase1 / phase2completednot on this map

An Open-Label, Phase 1/2, Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 in Patients With Progressive Advanced Castration-Resistant Prostate Cancer

TypeinterventionalSponsorAragon Pharmaceuticals, Inc.Ran2010 to 2025Enrolled127ConditionsProstate CancerArmsARN-509 (Phase 1), ARN-509 (Phase 2)
3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.

  1. Pooled it
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  5. Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide.Annals of oncology : official journal of the European Society for Medical Oncology · 2017
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 10 institutions in 2 countries.

Matthew R SmithMassachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA. Electronic address: smith.matthew@mgh.harvard.edu.
Emmanuel S AntonarakisSidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Charles J RyanUCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
William R BerryCancer Centers of North Carolina, Raleigh, NC, USA.
Neal D ShoreCarolina Urologic Research Center, Myrtle Beach, SC, USA.
Glenn LiuUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Joshi J AlumkalOregon Health & Science University, Knight Cancer Institute, Portland, OR, USA.
Celestia S HiganoUniversity of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Edna Chow ManevalAragon Pharmaceuticals, San Diego, CA, USA.
Rajesh BandekarJanssen Research & Development, Spring House, PA, USA.
Carla J de BoerJanssen Biologics, B.V., Leiden, The Netherlands.
Margaret K YuJanssen Research & Development, Los Angeles, CA, USA.
Dana E RathkopfMemorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Janssen (United States) · USCarolina Urologic Research Center · USFred Hutch Cancer Center · USHarvard University · USJanssen (Netherlands) · NLMemorial Sloan Kettering Cancer Center · USOregon Health & Science University · USSidney Kimmel Comprehensive Cancer Center · USUCSF Helen Diller Family Comprehensive Cancer Center · USUniversity of Wisconsin Carbone Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundApalutamide 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.

objectiveTo evaluate the activity and safety of apalutamide in patients with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC). DESIGN, SETTING, AND

participantsWe 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).

interventionPatients 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.

conclusionsIn 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 registrationClinicalTrials.gov identifier NCT01171898.

Indexed as

AgedAged, 80 and overAndrogen Receptor AntagonistsDisease-Free SurvivalHumansKallikreinsMaleMiddle AgedNeoplasm GradingProstate-Specific AntigenProstatic Neoplasms, Castration-ResistantThiohydantoinsTreatment OutcomeAndrogen Receptor AntagonistsapalutamideKallikreinsKLK3 protein, humanProstate-Specific AntigenThiohydantoinsAntitumor activityApalutamideCastration-resistant prostate cancerSafety

Identifiers

PMID27160947
PMCPMC5568792
OpenAlexW2346677152

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.