ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer
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- Andrew J. Armstrong
- Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC
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- Russell Z. Szmulewitz
- The University of Chicago, Chicago, IL
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- Daniel P. Petrylak
- Yale Cancer Center, New Haven, CT
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- Jeffrey Holzbeierlein
- The University of Kansas Medical Center, Kansas City, KS
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- Arnauld Villers
- Lille University, Lille, France
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- Arun Azad
- Monash Health, Melbourne, Victoria, Australia
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- Antonio Alcaraz
- Hospital Clinic of Barcelona, Barcelona, Spain
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- Boris Alekseev
- Hertzen Moscow Cancer Research Institute, Moscow, Russia
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- Taro Iguchi
- Osaka City University Graduate School of Medicine, Osaka, Japan
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- Neal D. Shore
- Carolina Urologic Research Center, Myrtle Beach, SC
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- Brad Rosbrook
- Pfizer, San Diego, CA
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- Jennifer Sugg
- Astellas Pharma, Northbrook, IL
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- Benoit Baron
- Astellas Pharma, Leiden, the Netherlands
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- Lucy Chen
- Astellas Pharma, Northbrook, IL
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- Arnulf Stenzl
- Eberhard Karls University of Tübingen, Tübingen, Germany
Abstract
<jats:sec><jats:title>PURPOSE</jats:title><jats:p> Enzalutamide, a potent androgen-receptor inhibitor, has demonstrated significant benefits in metastatic and nonmetastatic castration-resistant prostate cancer. We evaluated the efficacy and safety of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC). </jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p> ARCHES (ClinicalTrials.gov identifier: NCT02677896 ) is a multinational, double-blind, phase III trial, wherein 1,150 men with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg/day) or placebo, plus androgen deprivation therapy (ADT), stratified by disease volume and prior docetaxel chemotherapy. The primary end point was radiographic progression-free survival. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> As of October 14, 2018, the risk of radiographic progression or death was significantly reduced with enzalutamide plus ADT versus placebo plus ADT (hazard ratio, 0.39; 95% CI, 0.30 to 0.50; P < .001; median not reached v 19.0 months). Similar significant improvements in radiographic progression-free survival were reported in prespecified subgroups on the basis of disease volume and prior docetaxel therapy. Enzalutamide plus ADT significantly reduced the risk of prostate-specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event, castration resistance, and reduced risk of pain progression. More men achieved an undetectable prostate-specific antigen level and/or an objective response with enzalutamide plus ADT ( P < .001). Patients in both treatment groups reported a high baseline level of quality of life, which was maintained over time. Grade 3 or greater adverse events were reported in 24.3% of patients who received enzalutamide plus ADT versus 25.6% of patients who received placebo plus ADT, with no unexpected adverse events. </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> Enzalutamide with ADT significantly reduced the risk of metastatic progression or death over time versus placebo plus ADT in men with mHSPC, including those with low-volume disease and/or prior docetaxel, with a safety analysis that seems consistent with the safety profile of enzalutamide in previous clinical trials in castration-resistant prostate cancer. </jats:p></jats:sec>
Journal
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- Journal of Clinical Oncology
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Journal of Clinical Oncology 37 (32), 2974-2986, 2019-11-10
American Society of Clinical Oncology (ASCO)
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Details 詳細情報について
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- CRID
- 1362262945038791808
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- ISSN
- 15277755
- 0732183X
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- Data Source
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- Crossref