Evidence map›Paper›PMID 33636027›Full record

Trial reportThe Prostate2021

Nivolumab plus ipilimumab, with or without enzalutamide, in AR-V7-expressing metastatic castration-resistant prostate cancer: A phase-2 nonrandomized clinical trial.

Eugene Shenderov, Karim Boudadi, Wei Fu, Hao Wang, Rana Sullivan, Alice Jordan, Donna Dowling, Rana Harb, Joseph Schonhoft, Adam Jendrisak and 7 more

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Prostate, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02601014 (Biomarker-Driven Phase-2 Study of Combined Immune Checkpoint Blockade for AR-V7-Expressing Metastatic Castration-Resistant Prostate Cancer), which is not on this map. Cited by 50 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 7 pooled it
7.9field-weighted citation impact, top 2% 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.

NCT02601014 phase2completednot on this map

Biomarker-Driven Phase-2 Study of Combined Immune Checkpoint Blockade for AR-V7-Expressing Metastatic Castration-Resistant Prostate Cancer (STARVE-PC)

TypeinterventionalSponsorSidney Kimmel Comprehensive Cancer Center at Johns HopkinsRan2016 to 2021Enrolled32ConditionsProstate Cancer, Recurrent Prostate Carcinoma, Stage IV Prostate AdenocarcinomaArmsIpilimumab, Nivolumab, Enzalutamide
3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 7 syntheses or guidelines pooled it, 65 citations in OpenAlex.

  1. Pooled it
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  10. Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Trial
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  14. Evaluation of Tissue from Patients with Prostate Cancer Identifies B7-H3 as an Androgen-Regulated, Broadly Expressed, Combinatorial Therapeutic Target.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
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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

17 authors at 4 institutions in 1 country.

Eugene ShenderovDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0001-9886-8542
Karim BoudadiDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Wei FuDepartment of Oncology Biostatistics and Bioinformatics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Hao WangDepartment of Oncology Biostatistics and Bioinformatics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0001-6489-6940
Rana SullivanDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Alice JordanDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Donna DowlingDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Rana HarbDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Joseph SchonhoftEpic Sciences Inc., San Diego, California, USA.
Adam JendrisakEpic Sciences Inc., San Diego, California, USA.
Michael A CarducciDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Mario A EisenbergerDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
James R EshlemanDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jun LuoDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Charles G DrakeDepartment of Hematology/Oncology, Columbia University Medical Center, New York, New York, USA.
Drew M PardollDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Emmanuel S AntonarakisDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0003-0031-9655
Johns Hopkins University · USBloomberg (United States) · USEpic Sciences (United States) · USColumbia University Irving Medical Center · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
NCI NIH HHS P30 CA006973NIH HHS P30 CA006973
6 · The paper itself

Abstract

backgroundAR-V7-positive metastatic prostate cancer is a lethal phenotype with few treatment options and poor survival.

methodsThe two-cohort nonrandomized Phase 2 study of combined immune checkpoint blockade for AR-V7-expressing metastatic castration-resistant prostate cancer (STARVE-PC) evaluated nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg), without (Cohort 1) or with (Cohort 2) the anti-androgen enzalutamide. Co-primary endpoints were safety and prostate-specific antigen (PSA) response rate. Secondary endpoints included time-to-PSA-progression-free survival (PSA-PFS), time-to-clinical/radiographic-PFS, objective response rate (ORR), PFS lasting greater than 24 weeks, and overall survival (OS).

resultsThirty patients were treated with ipilimumab plus nivolumab (N = 15, Cohort 1, previously reported), or ipilimumab plus nivolumab and enzalutamide (N = 15, Cohort 2) in patients previously progressing on enzalutamide monotherapy. PSA response rate was 2/15 (13%) in cohort 1 and 0/15 in cohort 2, ORR was 2/8 (25%) in Cohort 1 and 0/9 in Cohort 2 in those with measureable disease, median PSA-PFS was 3.0 (95% confidence interval [CI]: 2.1-NR) in cohort 1 and 2.7 (95% CI: 2.1-5.9) months in cohort 2, and median PFS was 3.7 (95% CI: 2.8-7.5) in cohort 1 and 2.9 (95% CI: 1.3-5.8) months in cohort 2. Three of 15 patients in cohort 1 (20%, 95% CI: 7.1%-45.2%) and 4/15 patients (26.7%, 95% CI: 10.5%-52.4%) in cohort 2 achieved a durable PFS lasting greater than 24 weeks. Median OS was 8.2 (95% CI: 5.5-10.4) in cohort 1 and 14.2 (95% CI: 8.5-NA) months in cohort 2. Efficacy results were not statistically different between cohorts. Grade-3/4 adverse events occurred in 7/15 cohort 1 patients (46%) and 8/15 cohort 2 patients (53%). Combined cohort (N = 30) baseline alkaline phosphatase and cytokine analysis suggested improved OS for patients with lower alkaline phosphatase (hazards ratio [HR], 0.30; 95% CI: 0.11-0.82), lower circulating interleukin-7 (IL-7) (HR, 0.24; 95% Cl: 0.06-0.93) and IL-6 (HR, 0.13; 95% Cl: 0.03-0.52) levels, and higher circulating IL-17 (HR, 4.53; 95% CI: 1.47-13.93) levels. There was a trend towards improved outcomes in men with low sPD-L1 serum levels.

conclusionNivolumab plus ipilimumab demonstrated only modest activity in patients with AR-V7-expressing prostate cancer, and was not sufficient to justify further exploration in unselected patients. Stratification by baseline alkaline phosphatase and cytokines (IL-6, -7, and -17) may be prognostic for outcomes to immunotherapy.

Indexed as

Prostatic Neoplasms, Castration-ResistantAndrogen AntagonistsAntineoplastic AgentsBenzamidesDrug Therapy, CombinationHumansImmune Checkpoint InhibitorsIpilimumabMaleNitrilesNivolumabPhenylthiohydantoinPrognosisProtein IsoformsReceptors, AndrogenTreatment OutcomeAndrogen AntagonistsAntineoplastic AgentsBenzamidesenzalutamideImmune Checkpoint InhibitorsIpilimumabNitrilesNivolumabPhenylthiohydantoinProtein IsoformsReceptors, Androgenenzalutamideimmunotherapyipilimumabnivolumabprognostic biomarkerprostatic cancer

Identifiers

PMID33636027
PMCPMC8018565
OpenAlexW3129719839

What OpenQuestion holds

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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.