Evidence map›Paper›PMID 28171710›Full record

Trial reportCancer2017

Clinical outcomes and survival surrogacy studies of prostate-specific antigen declines following enzalutamide in men with metastatic castration-resistant prostate cancer previously treated with docetaxel.

Andrew J Armstrong, Fred Saad, De Phung, Carl Dmuchowski, Neal D Shore, Karim Fizazi, Mohammad Hirmand, David Forer, Howard I Scher, Johann De Bono

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 3 pooled it
4.7field-weighted citation impact, top 5% 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.

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

20 citing papers in PubMed, 3 syntheses or guidelines pooled it, 38 citations in OpenAlex.

  1. Pooled it
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  15. Consensus on management of castration-resistant prostate cancer on behalf of the Urological Tumours Working Group (URONCOR) of the Spanish Society of Radiation Oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019
    Article
  16. 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 at 8 institutions in 5 countries.

Andrew J ArmstrongDuke Cancer Institute, Durham, North Carolina.
Fred SaadCentre Hospitalier de l'Université de Montréal and CRCHUM, Montreal, Quebec, Canada.
De PhungAstellas Pharma, Inc., Leiden, Netherlands.
Carl DmuchowskiAstellas Pharma, Inc., Northbrook, Illinois.
Neal D ShoreCarolina Urologic Research Center, Myrtle Beach, South Carolina.
Karim FizaziInstitut Gustave Roussy, University of Paris Sud, Paris, France.
Mohammad HirmandMedivation, Inc., San Francisco, California.
David ForerMedivation, Inc., San Francisco, California.
Howard I ScherSidney Kimmel Center for Prostate and Urologic Cancers and Memorial Sloan-Kettering Cancer Center, New York, New York.
Johann De BonoInstitute of Cancer Research, London, UK.
Astellas Pharma (Netherlands) · NLAstellas Pharma (United States) · USCarolina Urologic Research Center · USCentre Hospitalier de l’Université de Montréal · CADuke Cancer InstituteInstitute of Cancer Research · GBInstitut Gustave Roussy · FRMemorial Sloan Kettering 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

backgroundIn the AFFIRM trial, enzalutamide significantly increased overall survival (OS) for men with metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy versus placebo and significantly decreased prostate-specific antigen (PSA) levels. The goal of this post hoc analysis was to associate levels of PSA decline from baseline after enzalutamide with clinical outcomes in the postchemotherapy mCRPC setting.

methodsMen in the AFFIRM trial (n = 1199) were grouped by maximal PSA decline in the first 90 days of treatment. Kaplan-Meier estimates evaluated the association of defined PSA changes from baseline with OS, progression-free survival (PFS), radiographic PFS (rPFS), and pain response. Each PSA decline category was assessed for OS surrogacy using Prentice criteria, proportion of treatment effect explained (PTE), and proportion of variation explained.

resultsMen treated with enzalutamide had improved OS (hazard ratio, 0.63; P < .001) and higher rates of PSA decline (odds ratio, >19.0; P < .001) versus placebo. PSA declines of any, ≥30%, ≥50%, and ≥90% with enzalutamide were strongly associated with greater OS, PSA PFS, rPFS (P < .001), and pain response (P < .026) versus PSA increase/no decline. Any, ≥30%, and ≥50% declines in PSA resulted in the PTE range of 1.07-1.29, where treatment was no longer significant after adjustment for decline measures (P > .20).

conclusionsPSA declines of any, ≥30%, and ≥50% following enzalutamide were associated with greater clinical and pain response and improvements in PFS and OS. Surrogacy of PSA decline for OS was not fully established, possibly due to lack of PSA declines with placebo, and discordant results between PSA and imaging responses over time, and because some declines were not durable due to rapid resistance development. However, a lack of PSA decline by 90 days following enzalutamide treatment was a poor prognosis indicator in this setting. Conclusions from sensitivity analyses of maximal PSA decline from baseline over the entire treatment period are consistent with PSA declines restricted to the first 90 days. Cancer 2017;123:2303-2311. © 2017 American Cancer Society.

Indexed as

Antineoplastic AgentsBenzamidesCarcinomaDisease-Free SurvivalDocetaxelDouble-Blind MethodHumansKallikreinsKaplan-Meier EstimateMaleNitrilesPhenylthiohydantoinProportional Hazards ModelsProstate-Specific AntigenProstatic Neoplasms, Castration-ResistantSurvival RateAntineoplastic AgentsBenzamidesDocetaxelenzalutamideKallikreinsKLK3 protein, humanNitrilesPhenylthiohydantoinProstate-Specific AntigenTaxoidsenzalutamidemetastatic castration-resistant prostate cancerprostate-specific antigensurrogate endpointsurvival

Identifiers

PMID28171710
PMCPMC5484320
OpenAlexW2586949432

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.