Evidence map›Paper›PMID 27429197›Full record

Trial reportOncotarget2016

Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer.

Julie N Graff, Joshi J Alumkal, Charles G Drake, George V Thomas, William L Redmond, Mohammad Farhad, Jeremy P Cetnar, Frederick S Ey, Raymond C Bergan, Rachel Slottke and 1 more

3 registry-linked trialsOpen access · diamondAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Oncotarget, 2016. 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 204 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
204citing papers in PubMed, 10 pooled it
27.9field-weighted citation impact, top 1% 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.

NCT03770455 phase2terminatednot on this mapstarted 2019, after this paper: background citation

PDL-1 Inhibition With Avelumab and Concurrent Second-generation ADT in African Americans With Castrate-resistant Metastatic Prostate Cancer

TypeinterventionalSponsorJodi Layton, MDRan2019 to 2021Enrolled8ConditionsMetastatic Castration-resistant Prostate CancerArmsAvelumab, 2nd generation ADT (abiraterone or enzalutamide)
NCT03835533 phase1completednot on this mapstarted 2019, after this paper: background citation

A Multicenter, Open-Label, Exploratory Platform Study to Evaluate Biomarkers and Immunotherapy Combinations for the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer

TypeinterventionalSponsorParker Institute for Cancer ImmunotherapyRan2019 to 2022Enrolled43ConditionsMetastatic Castration-resistant Prostate CancerArmsNKTR-214 (Cohort A), Nivolumab (Cohort A, B and C), Stereotactic body radiation therapy (SBRT) (Cohort B), CDX-301 (Cohort B and C), Poly-ICLC (Cohort B)
NCT04019964 phase2completednot on this mapstarted 2020, after this paper: background citation

Nivolumab as a Non-Castrating Therapy for MMR-deficient and CDK12- Altered Prostate Cancer With PSA Recurrence After Local Therapy

TypeinterventionalSponsorSidney Kimmel Comprehensive Cancer Center at Johns HopkinsRan2020 to 2025Enrolled8ConditionsProstate Cancer, Recurrent Prostate CancerArmsNivolumab
3 · Its place in the literature

Who cites it

204 citing papers in PubMed, 10 syntheses or guidelines pooled it, 356 citations in OpenAlex.

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  18. Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020
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144 more citing papers are in PubMed but not listed here.

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

11 authors at 4 institutions in 1 country.

Julie N GraffDivision of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Joshi J AlumkalDivision of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Charles G DrakeSidney Kimmel Comprehensive Cancer Center and the Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
George V ThomasPathology and Laboratory Medicine, Oregon Health and Science University, Portland, OR, USA.
William L RedmondRobert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR, USA.
Mohammad FarhadRobert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR, USA.
Jeremy P CetnarDivision of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Frederick S EyDivision of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Raymond C BerganDivision of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Rachel SlottkeDivision of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Tomasz M BeerDivision of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Oregon Health & Science University · USCancer Research Center · USProvidence Portland Medical Center · USSidney Kimmel Comprehensive Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

While programmed cell death 1 (PD-1) inhibitors have shown clear anti-tumor efficacy in several solid tumors, prior results in men with metastatic castration resistant prostate cancer (mCRPC) showed no evidence of activity. Here we report unexpected antitumor activity seen in mCRPC patients treated with the anti-PD-1 antibody pembrolizumab. Patients with evidence of progression on enzalutamide were treated with pembrolizumab 200 mg IV every 3 weeks for 4 doses; pembrolizumab was added to standard dose enzalutamide. Three of the first ten patients enrolled in this ongoing phase II trial experienced rapid prostate specific antigen (PSA) reductions to ≤ 0.2 ng/ml. Two of these three patients had measurable disease upon study entry; both achieved a partial response. There were three patients with significant immune-related adverse events. One had grade 2 myositis, one had grade 3 hypothyroidism, and one had grade 2 hypothyroidism. None of these patients had a response. Two of the three responders had a baseline tumor biopsy. Immunohistochemistry from those biopsies showed the presence of CD3+, CD8+, and CD163+ leukocyte infiltrates and PD-L1 expression. Genetic analysis of the two responders revealed markers of microsatellite instability in one. The surprising and robust responses seen in this study should lead to re-examination of PD-1 inhibition in prostate cancer.

Indexed as

AgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBenzamidesDrug Administration ScheduleDrug Resistance, NeoplasmHumansHypothyroidismMaleMiddle AgedMyositisNeoplasm MetastasisNitrilesPhenylthiohydantoinProgrammed Cell Death 1 ReceptorAntibodies, Monoclonal, HumanizedBenzamidesenzalutamideNitrilespembrolizumabPhenylthiohydantoinProgrammed Cell Death 1 ReceptorProstate-Specific AntigenenzalutamideImmune responseImmunityImmunology and Microbiology SectionimmunotherapyPD-1prostate cancer

Identifiers

PMID27429197
PMCPMC5288150
OpenAlexW2463867199

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.