Evidence map›Paper›PMID 33664086›Full record

Trial reportJournal for immunotherapy of cancer2021

Clinical and immunologic impact of short-course enzalutamide alone and with immunotherapy in non-metastatic castration sensitive prostate cancer.

Ravi A Madan, Fatima Karzai, Renee N Donahue, Munjid Al-Harthy, Marijo Bilusic, Inger I Rosner, Harpreet Singh, Philip M Arlen, Marc R Theoret, Jennifer L Marté and 12 more

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01875250 (A Phase II Trial of Enzalutamide in Combination With PSA-TRICOM in Patients With Non-Metastatic Castration Sensitive Prostate Cancer), which is not on this map. Cited by 26 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 2 pooled it
2.2field-weighted citation impact, top 12% 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.

NCT01875250 phase2completednot on this map

A Phase II Trial of Enzalutamide in Combination With PSA-TRICOM in Patients With Non-Metastatic Castration Sensitive Prostate Cancer

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2013 to 2020Enrolled38ConditionsProstate CancerArmsPROSTVAC-F (Fowlpox)/TRICOM, PROSTVAC-V (Vaccinia)/TRICOM, Enzalutamide (Xtandi)
3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 28 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
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  6. Review
  7. Article
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  11. Article
  12. Review
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  15. Immunotherapy in metastatic prostate cancer.Therapeutic advances in medical oncology · 2025
    Review
  16. Review
  17. Article
  18. Article
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  20. 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

22 authors at 2 institutions in 1 country.

Ravi A MadanGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA madanr@mail.nih.gov.ORCID 0000-0001-5106-8636
Fatima KarzaiGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Renee N DonahueLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Munjid Al-HarthyGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Marijo BilusicGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID 0000-0003-1020-689X
Inger I RosnerThe Center for Prostate Disease Research, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
Harpreet SinghGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Philip M ArlenGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Marc R TheoretGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Jennifer L MartéGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Lisa CordesGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID 0000-0003-3833-4084
Anna CouvillonGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Amy HankinGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Moniquea WilliamsGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Helen OwensGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Sarah E LochrinGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Cindy H ChauGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Seth SteinbergGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
William Douglas FiggGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
William DahutGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Jeffrey SchlomLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID 0000-0001-7932-4072
James L GulleyGenitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID 0000-0002-6569-2912
National Cancer Institute · USWalter Reed National Military Medical Center · US

Funding

Strategies for Therapeutic Cancer Vaccine Clinical TrialsZIABC010425 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SCHLOM, JEFFREY · 2009 to 2023
$13.7M
Drug Development for Prostate Cancer and other Metastatic ProcessesZIABC010547 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI FIGG, WILLIAM DOUGLAS · 2009 to 2025
$10.2M
Clinical trials employing cancer vaccine combination therapiesZIABC010945 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GULLEY, JAMES L. · 2009 to 2022
$9.6M
The Evaluation of Novel Therapeutics for Genitourinary MalignanciesZIASC010098 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI DAHUT, WILLIAM L. · 2009 to 2022
$7.6M
Evaluation of novel treatments in biochemically recurrent prostateZIABC011896 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MADAN, RAVI · 2019 to 2025
$3.6M
6 · The paper itself

Abstract

backgroundThe standard treatment for non-metastatic castration sensitive prostate cancer (nmCSPC) is androgen deprivation therapy (ADT) or surveillance. This study evaluated the potential synergy of immunotherapy and enzalutamide (without ADT) in nmCSPC. In addition, the immunologic impact of enzalutamide was also evaluated in men with normal testosterone.

methodsPatients with rising prostate-specific antigen (PSA) after definitive therapy, normal testosterone and no radiographic metastasis were randomized to enzalutamide for 3 months with/without PROSTVAC for 6 months. Thereafter, patients could be retreated with another 3 month course of enzalutamide when PSA returned to baseline. Immune profiles were evaluated in these patients.

resultsThirty-eight patients were randomized with a median PSA=4.38 ng/dL and PSA doubling time=4.1 months. No difference was observed between the two groups for PSA growth kinetics, but PSA responses to enzalutamide were noteworthy regardless of PROSTVAC. The median PSA decline after short-course enzalutamide without ADT/testosterone lowering therapy was 99% in both courses. The median time to PSA recovery to baseline after each 84-day course of enzalutamide was also noteworthy because of the duration of response after enzalutamide was discontinued. After the first and second 3 month cycle of enzalutamide, PSA recovery to baseline took a median 224 (range 84-1246) and 189 days (78-400), respectively. The most common adverse events related to the enzalutamide were grade 1 fatigue (71%) and grade 1 breast pain/nipple tenderness (81%). The only grade 3 toxicity was aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation in two patients. Enzalutamide was independently associated with immune changes, increasing natural killer cells, naïve-T cells, and decreasing myeloid-derived suppressor cells.

conclusionsThree months of enzalutamide without ADT induced substantial PSA control beyond the treatment period and was repeatable, perhaps representing an alternative to intermittent ADT in nmCSPC. In addition, enzalutamide was associated with immune changes that could be relevant as future immune combinations are developed. TRAIL REGISTRATION NUMBER: clinicaltrials.gov (NCT01875250).

Indexed as

AgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBenzamidesCancer VaccinesDrug Administration ScheduleHumansKallikreinsMaleMarylandMiddle AgedNitrilesPhenylthiohydantoinProstate-Specific AntigenProstatic Neoplasms, Castration-ResistantTestosteroneBenzamidesCancer VaccinesenzalutamideKallikreinsKLK3 protein, humanNitrilesPhenylthiohydantoinProstate-Specific AntigenPROSTVACTestosteroneimmunotherapykiller cellsmyeloid-derived suppressor cellsnaturalprostatic neoplasms

Identifiers

PMID33664086
PMCPMC7934713
OpenAlexW3134742221

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.