Evidence map›Paper›PMID 39134652›Full record

Trial reportProstate cancer and prostatic diseases2025

Pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer progressing on enzalutamide: cohorts 4 and 5 of the phase 2 KEYNOTE-199 study.

Julie N Graff, Christopher J Hoimes, Winald R Gerritsen, Ulka N Vaishampayan, Tony Elliott, Clara Hwang, Albert J Ten Tije, Aurelius Omlin, Raymond S McDermott, Yves Fradet and 15 more

Registry-linked trialAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Publisher
In one paragraph

Trial report in Prostate cancer and prostatic diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02787005 (Phase II Trial of Pembrolizumab), which is not on this map. Cited by 12 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 2 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.

NCT02787005 phase2completednot on this map

Phase II Trial of Pembrolizumab (MK-3475) in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-199)

TypeinterventionalSponsorMerck Sharp & Dohme LLCRan2016 to 2022Enrolled388ConditionsMetastatic Castration-resistant Prostate CancerArmsPembrolizumab
3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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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

25 authors.

Julie N GraffOregon Health and Science University, Portland, OR, USA. graffj@ohsu.edu.
Christopher J HoimesCase Comprehensive Cancer Center, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Winald R GerritsenRadboud University Medical Center, Nijmegen, Netherlands.
Ulka N VaishampayanUniversity of Michigan and Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Tony ElliottNHS Lothian, Edinburgh, UK.
Clara HwangHenry Ford Health System, Detroit, MI, USA.ORCID http://orcid.org/0000-0002-0998-323X
Albert J Ten TijeAmphia Hospital, Breda, Netherlands.
Aurelius OmlinOnkozentrum Zurich, University of Zurich and Tumorzentrum Hirslanden Zurich, Zurich, Switzerland.
Raymond S McDermottTallaght University Hospital, Dublin, Ireland.
Yves FradetCHU de Québec-Université Laval, Québec City, QC, Canada.
Scott T TagawaWeill Cornell Medical College, New York, NY, USA.ORCID http://orcid.org/0000-0003-2777-8587
Deepak KilariMedical College of Wisconsin, Milwaukee, WI, USA.
Cristiano FerrarioJewish General Hospital, Montreal, QC, Canada.
Hiroji UemuraYokohama City University Medical Center, Yokohama, Japan.
Robert J JonesUniversity of Glasgow, Glasgow, UK.ORCID http://orcid.org/0000-0002-2904-6980
Satoshi FukasawaChiba Cancer Center, Chiba, Japan.
Avivit PeerRambam Health Care Campus, Haifa, Israel.
Cuizhen NiuMSD China, Beijing, China.
Christian H PoehleinMerck & Co., Inc., Rahway, NJ, USA.
Ping QiuMerck & Co., Inc., Rahway, NJ, USA.
Leah SuttnerMerck & Co., Inc., Rahway, NJ, USA.
Ronald de WitErasmus University Medical Center, Rotterdam, Netherlands.ORCID http://orcid.org/0000-0002-1954-090X
Charles SchlossMerck & Co., Inc., Rahway, NJ, USA.
Johann S de BonoThe Royal Marsden Hospital NHS Foundation Trust and the Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0002-2034-595X
Emmanuel S AntonarakisThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-0031-9655

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundKEYNOTE-199 (NCT02787005) is a multicohort phase 2 study evaluating pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC). Results from cohorts 4 (C4) and 5 (C5) are presented.

methodsEligible patients had not received chemotherapy for mCRPC and had responded to enzalutamide prior to developing resistance as defined by Prostate Cancer Clinical Trials Working Group 3 guidelines. Patients with RECIST-measurable disease were enrolled in C4, and patients with bone-only or bone-predominant disease were enrolled in C5. All patients received pembrolizumab 200 mg every 3 weeks for ≤35 cycles with ongoing enzalutamide until progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate (ORR) per RECIST v1.1 by blinded independent central review in C4. Secondary end points included disease control rate (DCR), overall survival, and safety in each cohort and both cohorts combined.

resultsA total of 126 patients were treated (C4, n = 81; C5, n = 45). Median age was 72 years (range 43-92), and 87.3% had received ≥6 months of enzalutamide prior to study entry. Confirmed ORR was 12.3% (95% CI 6.1-21.5%) for C4. Median duration of response in C4 was 8.1 months (range, 2.5+ to 15.2), and 5 of these patients experienced an objective response lasting ≥6 months. DCR was 53.1% (95% CI 41.7-64.3%) in C4 and 51.1% (95% CI 35.8-66.3%) in C5. Median overall survival was 17.6 months (95% CI 14.0-22.6) in C4 and 20.8 months (95% CI 14.1-28.9) in C5. Grade ≥3 treatment-related adverse events occurred in 35 patients (27.8%); 2 patients in C4 died from immune-related adverse events (myasthenic syndrome and Guillain-Barré syndrome).

conclusionsThe addition of pembrolizumab to ongoing enzalutamide treatment in patients with mCRPC that progressed on enzalutamide after initial response demonstrated modest antitumor activity with a manageable safety profile. CLINICAL TRIAL REGISTRY AND ID: ClinicalTrials.gov, NCT02787005.

Indexed as

Antibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsPhenylthiohydantoinProstatic Neoplasms, Castration-ResistantAgedAged, 80 and overBenzamidesDisease ProgressionDrug Resistance, NeoplasmHumansMaleMiddle AgedNeoplasm MetastasisNitrilesAntibodies, Monoclonal, HumanizedBenzamidesenzalutamideNitrilespembrolizumabPhenylthiohydantoin

Identifiers

PMID39134652

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.