Evidence mapPaperPMID 35643841Full record

SynthesisEuropean journal of cancer (Oxford, England : 1990)2022

Statin and metformin use and outcomes in patients with castration-resistant prostate cancer treated with enzalutamide: A meta-analysis of AFFIRM, PREVAIL and PROSPER.

Anthony M Joshua, Andrew Armstrong, Megan Crumbaker, Howard I Scher, Johann de Bono, Bertrand Tombal, Maha Hussain, Cora N Sternberg, Silke Gillessen, Joan Carles and 6 more

3 registry-linked trialsOpen access · bronzeAbstract readMeta-Analysis
In one paragraph

Synthesis in European journal of cancer (Oxford, England : 1990), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
4.0field-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.

NCT00974311 phase3completednot on this map

Affirm: A Multinational Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy And Safety Study Of Oral Mdv3100 In Patients With Progressive Castration-resistant Prostate Cancer Previously Treated With Docetaxel Based Chemotherapy

TypeinterventionalSponsorPfizerRan2009 to 2017Enrolled1,199ConditionsCastration-Resistant Prostate CancerArmsEnzalutamide, Placebo
NCT01212991 phase3completednot on this map

Prevail: a multinational phase 3, randomized, double-blind, placebo-controlled efficacy and safety study of oral mdv3100 in chemotherapy-naïve patients with progressive metastatic prostate cancer who have failed androgen deprivation therapy

TypeinterventionalSponsorPfizerRan2010 to 2019Enrolled1,717ConditionsProstate CancerArmsEnzalutamide, Placebo
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
3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Dissecting the role of metformin in urogenital malignancies.Annals of medicine and surgery (2012) · 2025
    Article
  7. Article
  8. Review
  9. Cancers · 2024
    Review
  10. Prostate Cancer and the Mevalonate Pathway.International journal of molecular sciences · 2024
    Review
  11. Review
  12. Targeting lipid metabolism in metastatic prostate cancer.Therapeutic advances in medical oncology · 2023
    Review
  13. Review
  14. Review
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

16 authors at 13 institutions in 7 countries.

Anthony M JoshuaKinghorn Cancer Centre, St. Vincent's Hospital, Sydney, NSW, Australia. Electronic address: anthony.joshua@svha.org.au.
Andrew ArmstrongDuke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA.
Megan CrumbakerKinghorn Cancer Centre, St. Vincent's Hospital, Sydney, NSW, Australia.
Howard I ScherMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Johann de BonoThe Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, London, UK.
Bertrand TombalCliniques Universitaires Saint-Luc, Brussels, Belgium.
Maha HussainRobert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
Cora N SternbergEnglander Institute for Precision Medicine, Weill Cornell Medicine, Meyer Cancer Center, New York, NY, USA.
Silke GillessenOncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland.
Joan CarlesVall D'Hebron University Hospital, Vall D'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Karim FizaziInstitut Gustave Roussy, University of Paris Saclay, Villejuif, France.
Ping LinFormerly of Pfizer Inc., San Francisco, CA, USA.
William DugganPfizer Inc., Groton, CT, USA.
Jennifer SuggAstellas Pharma, Inc., Northbrook, IL, USA.
David RussellPfizer Inc., New York, NY, USA.
Tomasz M BeerOHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Pfizer (United States) · USSt Vincent's Hospital Sydney · AUAstellas Pharma (United States) · USCliniques Universitaires Saint-Luc · BECornell University · USDuke University · USInstitute of Oncology Research · CHMemorial Sloan Kettering Cancer Center · USNorthwestern University · USOregon Health & Science University · USRoyal Marsden NHS Foundation Trust · GBUniversité Paris-Saclay · FRVall d'Hebron Hospital Universitari · ES

Funding

The Patient-Reported Outcomes, Community-Engagement and Language (PRO-CEL) CoreP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · 1985 to 2025
$88.4M
SPORE in Prostate CancerP50CA092629 · SLOAN-KETTERING INSTITUTE FOR CANCER RES · 2001 to 2025
$16.9M
Medical Research Council MR/W018217/1NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA092629
6 · The paper itself

Abstract

backgroundStatins and metformin are commonly prescribed for patients, including those with prostate cancer. Preclinical and epidemiologic studies of each agent have suggested anti-cancer properties.

methodsPatient data from three randomised, double-blind, placebo-controlled, phase III studies evaluating enzalutamide (AFFIRM, PREVAIL and PROSPER) in patients with castration-resistant prostate cancer were included in this analysis. This post hoc, retrospective study examined the association of statin and metformin on radiographic progression-free survival (rPFS), metastasis-free survival (MFS), toxicity and overall survival (OS). After adjusting for available clinical prognostic variables, multivariate analyses were performed on pooled data from AFFIRM and PREVAIL, all three trials pooled, and each trial individually, to assess differential efficacy in these end-points associated with the baseline use of these medications.

resultsIn the multivariate analysis of the individual trials, OS and rPFS/MFS were not significantly influenced by statin or metformin use in AFFIRM or PROSPER. However, in PREVAIL, OS was significantly influenced by statin (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.59-0.89) and rPFS was significantly influenced by metformin (HR, 0.48; 95% CI 0.34-0.70). In pooled analyses, improved OS was significantly associated with statin use but not metformin use for AFFIRM+PREVAIL trials (HR 0.83; 95% CI 0.72-0.96) and AFFIRM+PREVAIL+PROSPER (HR 0.75; 95% CI 0.66-0.85).

conclusionsThe association between statin or metformin use and rPFS, MFS and OS was inconsistent across three trials. Analyses of all three trials pooled and AFFIRM+PREVAIL pooled revealed that statin but not metformin use was significantly associated with a reduced risk of death in enzalutamide-treated patients. Additional prospective, controlled studies are warranted. CLINICAL

trial registrationAFFIRM (NCT00974311), PREVAIL (NCT01212991) and PROSPER (NCT02003924).

Indexed as

Antineoplastic AgentsHydroxymethylglutaryl-CoA Reductase InhibitorsMetforminProstatic Neoplasms, Castration-ResistantBenzamidesDisease-Free SurvivalHumansMaleNitrilesPhenylthiohydantoinProspective StudiesRandomized Controlled Trials as TopicRetrospective StudiesTreatment OutcomeAntineoplastic AgentsBenzamidesenzalutamideHydroxymethylglutaryl-CoA Reductase InhibitorsMetforminNitrilesPhenylthiohydantoinCastration-resistant prostate cancerEnzalutamideMetforminOverall survivalRadiographic progression-free survivalStatin

Identifiers

PMID35643841
PMCPMC10394474
OpenAlexW4281569406

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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 Socratic graph.