Evidence map›Paper›PMID 39168093›Full record

Trial reportCell reports. Medicine2024

HSD3B1 genotype and outcomes in metastatic hormone-sensitive prostate cancer with androgen deprivation therapy and enzalutamide: ARCHES.

Nima Sharifi, Arun A Azad, Mona Patel, Jason W D Hearn, Michele Wozniak, Fabian Zohren, Jennifer Sugg, Gabriel P Haas, Arnulf Stenzl, Andrew J Armstrong

Abstract readRandomized Controlled TrialClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Trial
  2. Article
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  4. Article
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  6. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Nima SharifiDesai Sethi Urology Institute and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: nimasharifi@miami.edu.
Arun A AzadDepartment of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Mona PatelDesai Sethi Urology Institute and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
Jason W D HearnDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Michele WozniakAstellas Pharma Inc., Northbrook, IL, USA.
Fabian ZohrenPfizer Inc., San Diego, CA, USA.
Jennifer SuggAstellas Pharma Inc., Northbrook, IL, USA.
Gabriel P HaasAstellas Pharma Inc., Northbrook, IL, USA.
Arnulf StenzlDepartment of Urology, University Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany.
Andrew J ArmstrongDivisions of Medical Oncology and Urology, Duke Cancer Institute Center for Prostate & Urologic Cancers, Durham, NC, USA.

Funding

Elucidating a novel molecular biomarker for castration-resistant prostate cancerR01CA172382 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Nima Sharifi · 2012 to 2026
$5.2M
Insulin Stimulated Production Of Nitric Oxide In Vascular EndotheliumZ01AT000001 · NCCIH · NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH · PI QUON, MICHAEL J. · 2002 to 2008
$2.4M
Interactions of Androgen Production, Uptake and Metabolism on outcome in Castration Resistant Prostate CancerR01CA249279 · NCI · UNIVERSITY OF MINNESOTA · PI HALABI, SUSAN, SHARIFI, NIMA · 2021 to 2024
$2.1M
Aberrant tumor metabolism that enables AR antagonist-resistant prostate cancerR01CA236780 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI SHARIFI, NIMA · 2020 to 2024
$1.8M
CYP17A1-independent androgen synthesis and prostate cancer resistance to next-generation hormonal therapyR01CA261995 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Nima Sharifi · 2022 to 2026
$1.8M
Intramural NIH HHS Z01 AT000001NCI NIH HHS R01 CA172382NCI NIH HHS R01 CA236780NCI NIH HHS R01 CA249279NCI NIH HHS R01 CA261995
6 · The paper itself

Abstract

HSD3B1 encodes 3β-hydroxysteroid dehydrogenase-1, which converts adrenal dehydroepiandrosterone to 5α-dihydrotestosterone and is inherited in adrenal-permissive (AP) or adrenal-restrictive forms. The AP allele is linked to castration resistance, mainly in low-volume tumors. Here, we investigate the association of HSD3B1 alleles with outcomes in ARCHES, a multinational, double-blind, randomized, placebo-controlled phase 3 trial that demonstrated clinical benefit with enzalutamide plus androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC) compared to those treated with placebo plus ADT. There are no significant differences between genotypes for clinical efficacy endpoints. Enzalutamide significantly improves radiographic progression-free survival and overall survival vs. placebo irrespective of HSD3B1 status. Men with the AP genotype have higher post-progression mortality and treatment-emergent adverse events, including hypertension, cardiovascular events, and gynecomastia, but a lower fracture rate. Overall, enzalutamide is beneficial in men with mHSPC independent of the HSD3B1 genotype. Inherited polymorphisms of HSD3B1 may account for differential toxicities.

Indexed as

Androgen AntagonistsBenzamidesGenotypeMultienzyme ComplexesNitrilesPhenylthiohydantoinProgesterone ReductaseProstatic NeoplasmsSteroid IsomerasesAgedAllelesDouble-Blind MethodHumansMaleMiddle AgedNeoplasm Metastasis3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomeraseAndrogen AntagonistsBenzamidesenzalutamideMultienzyme ComplexesNitrilesPhenylthiohydantoinProgesterone ReductaseSteroid IsomerasesandrogensenzalutamideHSD3B1metabolismmetastatic hormone-sensitive prostate cancer

Identifiers

PMID39168093
PMCPMC11384952

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Registered trials

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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.