Evidence map›Paper›PMID 29949494›Full record

Trial reportThe New England journal of medicine2018

Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer.

Maha Hussain, Karim Fizazi, Fred Saad, Per Rathenborg, Neal Shore, Ubirajara Ferreira, Petro Ivashchenko, Eren Demirhan, Katharina Modelska, De Phung and 2 more

2 registry-linked trialsAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 485 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
485citing papers in PubMed, 10 pooled it
–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.

NCT02003924 phase3completednot on this map

Prosper: a multinational, phase 3, randomized, double-blind, placebo-controlled, efficacy and safety study of enzalutamide in patients with nonmetastatic castration-resistant prostate cancer

TypeinterventionalSponsorPfizerRan2013 to 2025Enrolled1,401ConditionsNonmetastatic Castration-Resistant Prostate Cancer, Prostate Cancer, Cancer of the ProstateArmsEnzalutamide, Placebo
NCT04335682 phase2completednot on this mapstarted 2021, after this paper: background citation

A Randomized Phase II Study of Androgen Receptor Directed Therapy on COGnitive Function in Patients Treated With Darolutamide or Enzalutamide (ARACOG)

TypeinterventionalSponsorAlliance Foundation Trials, LLC.Ran2021 to 2026Enrolled111ConditionsMetastatic Prostate Cancer, Prostate Cancer Metastatic, Prostate Cancer, Castrate Resistant Prostate CancerArmsDarolutamide, Enzalutamide
3 · Its place in the literature

Who cites it

485 citing papers in PubMed, 10 syntheses or guidelines pooled it.

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  11. Radiographic Progression With and Without Prostate-Specific Antigen Rise in Patients With Advanced Prostate Cancer Treated With Enzalutamide.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
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425 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Maha HussainFrom the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago (M.H.), and Astellas Pharma, Northbrook (D.P., A.K.) - both in Illinois; Institut Gustave Roussy, University of Paris Sud, Villejuif, France (K.F.); the University of Montreal Hospital Center, Montreal (F.S.); Herlev Hospital, Herlev, Denmark (P.R.); Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); State University of Campinas (Unicamp), Campinas, Brazil (U.F.); Kiev City Clinical Hospital 3, Kiev, Ukraine (P.I.); Pfizer, San Francisco (E.D., K.M.); and the Department of Medical Oncology, San Camillo Forlanini Hospital, Rome (C.N.S.).
Karim FizaziFrom the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago (M.H.), and Astellas Pharma, Northbrook (D.P., A.K.) - both in Illinois; Institut Gustave Roussy, University of Paris Sud, Villejuif, France (K.F.); the University of Montreal Hospital Center, Montreal (F.S.); Herlev Hospital, Herlev, Denmark (P.R.); Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); State University of Campinas (Unicamp), Campinas, Brazil (U.F.); Kiev City Clinical Hospital 3, Kiev, Ukraine (P.I.); Pfizer, San Francisco (E.D., K.M.); and the Department of Medical Oncology, San Camillo Forlanini Hospital, Rome (C.N.S.).
Fred SaadFrom the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago (M.H.), and Astellas Pharma, Northbrook (D.P., A.K.) - both in Illinois; Institut Gustave Roussy, University of Paris Sud, Villejuif, France (K.F.); the University of Montreal Hospital Center, Montreal (F.S.); Herlev Hospital, Herlev, Denmark (P.R.); Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); State University of Campinas (Unicamp), Campinas, Brazil (U.F.); Kiev City Clinical Hospital 3, Kiev, Ukraine (P.I.); Pfizer, San Francisco (E.D., K.M.); and the Department of Medical Oncology, San Camillo Forlanini Hospital, Rome (C.N.S.).
Per RathenborgFrom the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago (M.H.), and Astellas Pharma, Northbrook (D.P., A.K.) - both in Illinois; Institut Gustave Roussy, University of Paris Sud, Villejuif, France (K.F.); the University of Montreal Hospital Center, Montreal (F.S.); Herlev Hospital, Herlev, Denmark (P.R.); Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); State University of Campinas (Unicamp), Campinas, Brazil (U.F.); Kiev City Clinical Hospital 3, Kiev, Ukraine (P.I.); Pfizer, San Francisco (E.D., K.M.); and the Department of Medical Oncology, San Camillo Forlanini Hospital, Rome (C.N.S.).
Neal ShoreFrom the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago (M.H.), and Astellas Pharma, Northbrook (D.P., A.K.) - both in Illinois; Institut Gustave Roussy, University of Paris Sud, Villejuif, France (K.F.); the University of Montreal Hospital Center, Montreal (F.S.); Herlev Hospital, Herlev, Denmark (P.R.); Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); State University of Campinas (Unicamp), Campinas, Brazil (U.F.); Kiev City Clinical Hospital 3, Kiev, Ukraine (P.I.); Pfizer, San Francisco (E.D., K.M.); and the Department of Medical Oncology, San Camillo Forlanini Hospital, Rome (C.N.S.).
Ubirajara FerreiraFrom the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago (M.H.), and Astellas Pharma, Northbrook (D.P., A.K.) - both in Illinois; Institut Gustave Roussy, University of Paris Sud, Villejuif, France (K.F.); the University of Montreal Hospital Center, Montreal (F.S.); Herlev Hospital, Herlev, Denmark (P.R.); Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); State University of Campinas (Unicamp), Campinas, Brazil (U.F.); Kiev City Clinical Hospital 3, Kiev, Ukraine (P.I.); Pfizer, San Francisco (E.D., K.M.); and the Department of Medical Oncology, San Camillo Forlanini Hospital, Rome (C.N.S.).
Petro IvashchenkoFrom the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago (M.H.), and Astellas Pharma, Northbrook (D.P., A.K.) - both in Illinois; Institut Gustave Roussy, University of Paris Sud, Villejuif, France (K.F.); the University of Montreal Hospital Center, Montreal (F.S.); Herlev Hospital, Herlev, Denmark (P.R.); Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); State University of Campinas (Unicamp), Campinas, Brazil (U.F.); Kiev City Clinical Hospital 3, Kiev, Ukraine (P.I.); Pfizer, San Francisco (E.D., K.M.); and the Department of Medical Oncology, San Camillo Forlanini Hospital, Rome (C.N.S.).
Eren DemirhanFrom the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago (M.H.), and Astellas Pharma, Northbrook (D.P., A.K.) - both in Illinois; Institut Gustave Roussy, University of Paris Sud, Villejuif, France (K.F.); the University of Montreal Hospital Center, Montreal (F.S.); Herlev Hospital, Herlev, Denmark (P.R.); Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); State University of Campinas (Unicamp), Campinas, Brazil (U.F.); Kiev City Clinical Hospital 3, Kiev, Ukraine (P.I.); Pfizer, San Francisco (E.D., K.M.); and the Department of Medical Oncology, San Camillo Forlanini Hospital, Rome (C.N.S.).
Katharina ModelskaFrom the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago (M.H.), and Astellas Pharma, Northbrook (D.P., A.K.) - both in Illinois; Institut Gustave Roussy, University of Paris Sud, Villejuif, France (K.F.); the University of Montreal Hospital Center, Montreal (F.S.); Herlev Hospital, Herlev, Denmark (P.R.); Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); State University of Campinas (Unicamp), Campinas, Brazil (U.F.); Kiev City Clinical Hospital 3, Kiev, Ukraine (P.I.); Pfizer, San Francisco (E.D., K.M.); and the Department of Medical Oncology, San Camillo Forlanini Hospital, Rome (C.N.S.).
De PhungFrom the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago (M.H.), and Astellas Pharma, Northbrook (D.P., A.K.) - both in Illinois; Institut Gustave Roussy, University of Paris Sud, Villejuif, France (K.F.); the University of Montreal Hospital Center, Montreal (F.S.); Herlev Hospital, Herlev, Denmark (P.R.); Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); State University of Campinas (Unicamp), Campinas, Brazil (U.F.); Kiev City Clinical Hospital 3, Kiev, Ukraine (P.I.); Pfizer, San Francisco (E.D., K.M.); and the Department of Medical Oncology, San Camillo Forlanini Hospital, Rome (C.N.S.).
Andrew KrivoshikFrom the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago (M.H.), and Astellas Pharma, Northbrook (D.P., A.K.) - both in Illinois; Institut Gustave Roussy, University of Paris Sud, Villejuif, France (K.F.); the University of Montreal Hospital Center, Montreal (F.S.); Herlev Hospital, Herlev, Denmark (P.R.); Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); State University of Campinas (Unicamp), Campinas, Brazil (U.F.); Kiev City Clinical Hospital 3, Kiev, Ukraine (P.I.); Pfizer, San Francisco (E.D., K.M.); and the Department of Medical Oncology, San Camillo Forlanini Hospital, Rome (C.N.S.).
Cora N SternbergFrom the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago (M.H.), and Astellas Pharma, Northbrook (D.P., A.K.) - both in Illinois; Institut Gustave Roussy, University of Paris Sud, Villejuif, France (K.F.); the University of Montreal Hospital Center, Montreal (F.S.); Herlev Hospital, Herlev, Denmark (P.R.); Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); State University of Campinas (Unicamp), Campinas, Brazil (U.F.); Kiev City Clinical Hospital 3, Kiev, Ukraine (P.I.); Pfizer, San Francisco (E.D., K.M.); and the Department of Medical Oncology, San Camillo Forlanini Hospital, Rome (C.N.S.).

Funding

Targeting FOXA1-downstream pathways: a novel therapeutic strategy for castration-resistant prostate cancerP50CA180995 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ABDULKADIR, SARKI A., HUSSAIN, MAHA H · 2015 to 2025
$19.9M
NCI NIH HHS P50 CA180995
6 · The paper itself

Abstract

backgroundMen with nonmetastatic, castration-resistant prostate cancer and a rapidly rising prostate-specific antigen (PSA) level are at high risk for metastasis. We hypothesized that enzalutamide, which prolongs overall survival among patients with metastatic, castration-resistant prostate cancer, would delay metastasis in men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA level.

methodsIn this double-blind, phase 3 trial, we randomly assigned, in a 2:1 ratio, men with nonmetastatic, castration-resistant prostate cancer and a PSA doubling time of 10 months or less who were continuing androgen-deprivation therapy to receive enzalutamide (at a dose of 160 mg) or placebo once daily. The primary end point was metastasis-free survival (defined as the time from randomization to radiographic progression or as the time to death without radiographic progression).

resultsA total of 1401 patients (median PSA doubling time, 3.7 months) underwent randomization. As of June 28, 2017, a total of 219 of 933 patients (23%) in the enzalutamide group had metastasis or had died, as compared with 228 of 468 (49%) in the placebo group. The median metastasis-free survival was 36.6 months in the enzalutamide group versus 14.7 months in the placebo group (hazard ratio for metastasis or death, 0.29; 95% confidence interval, 0.24 to 0.35; P<0.001). The time to the first use of a subsequent antineoplastic therapy was longer with enzalutamide treatment than with placebo (39.6 vs. 17.7 months; hazard ratio, 0.21; P<0.001; such therapy was used in 15% vs. 48% of patients) as was the time to PSA progression (37.2 vs. 3.9 months; hazard ratio, 0.07; P<0.001; progression occurred in 22% vs. 69% of patients). At the first interim analysis of overall survival, 103 patients (11%) receiving enzalutamide and 62 (13%) receiving placebo had died. Adverse events of grade 3 or higher occurred in 31% of the patients receiving enzalutamide, as compared with 23% of those receiving placebo.

conclusionsAmong men with nonmetastatic, castration-resistant prostate cancer with a rapidly rising PSA level, enzalutamide treatment led to a clinically meaningful and significant 71% lower risk of metastasis or death than placebo. Adverse events were consistent with the established safety profile of enzalutamide. (Funded by Pfizer and Astellas Pharma; PROSPER ClinicalTrials.gov number, NCT02003924 .).

Indexed as

AdenocarcinomaAgedAged, 80 and overAntineoplastic AgentsBenzamidesDisease-Free SurvivalDouble-Blind MethodHumansKallikreinsKaplan-Meier EstimateMaleMiddle AgedNeoplasm MetastasisNitrilesPhenylthiohydantoinProstate-Specific AntigenAntineoplastic AgentsBenzamidesenzalutamideKallikreinsKLK3 protein, humanNitrilesPhenylthiohydantoinProstate-Specific Antigen

Identifiers

PMID29949494
PMCPMC8288034

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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.