Evidence map›Paper›PMID 32616555›Full record

Trial reportJournal for immunotherapy of cancer2020

A phase II single-arm study of pembrolizumab with enzalutamide in men with metastatic castration-resistant prostate cancer progressing on enzalutamide alone.

Julie N Graff, Tomasz M Beer, Joshi J Alumkal, Rachel E Slottke, William L Redmond, George V Thomas, Reid F Thompson, Mary A Wood, Yoshinobu Koguchi, Yiyi Chen and 4 more

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

Trial report in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02312557 (Addition of Pembrolizumab Upon Progression on Enzalutamide in Men With mCRPC), which is not on this map. Cited by 86 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 8 pooled it
9.7field-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.

NCT02312557 phase2active not recruitingnot on this map

Addition of Pembrolizumab Upon Progression on Enzalutamide in Men With mCRPC

TypeinterventionalSponsorOHSU Knight Cancer InstituteRan2014 to 2026Enrolled58ConditionsCastration-Resistant Prostate Carcinoma, Hormone-Resistant Prostate Cancer, PSA Progression, Recurrent Prostate CarcinomaArmsEnzalutamide, Laboratory Biomarker Analysis, Pembrolizumab
3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 8 syntheses or guidelines pooled it, 119 citations in OpenAlex.

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26 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

14 authors at 5 institutions in 1 country.

Julie N GraffDivision of Hospitalist and Specialty Medicine, Portland VA Medical Center, Portland, Oregon, USA graffj@ohsu.edu.
Tomasz M BeerKnight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
Joshi J AlumkalDepartment of Internal Medicine, University of Michigan Rogel Cancer Center, Ann Arbor, Michigan, USA.
Rachel E SlottkeKnight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
William L RedmondEarle A. Chiles Research Institute, Portland, Oregon, USA.ORCID 0000-0002-2572-1731
George V ThomasDepartment of Pathology and Laboratory Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Reid F ThompsonDivision of Hospitalist and Specialty Medicine, Portland VA Medical Center, Portland, Oregon, USA.
Mary A WoodDivision of Hospitalist and Specialty Medicine, Portland VA Medical Center, Portland, Oregon, USA.
Yoshinobu KoguchiEarle A. Chiles Research Institute, Portland, Oregon, USA.
Yiyi ChenBiostatistics Shared Resource, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
Emile LatourBiostatistics Shared Resource, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
Raymond C BerganKnight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
Charles G DrakeDepartment of Medicine, Oncology Division, Columbia University Medical Center, New York City, New York, USA.
Amy E MoranCell, Development & Cancer Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
Oregon Health & Science University · USProvidence Portland Medical Center · USColumbia University Irving Medical Center · USPortland VA Medical Center · USUniversity of Michigan · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCheckpoint inhibitors can induce profound anticancer responses, but programmed cell death protein-1 (PD-1) inhibition monotherapy has shown minimal activity in prostate cancer. A published report showed that men with prostate cancer who were resistant to the second-generation androgen receptor inhibitor enzalutamide had increased programmed death-ligand 1 (PD-L1) expression on circulating antigen-presenting cells. We hypothesized that the addition of PD-1 inhibition in these patients could induce a meaningful cancer response.

methodsWe evaluated enzalutamide plus the PD-1 inhibitor pembrolizumab in a single-arm phase II study of 28 men with metastatic castration-resistant prostate cancer (mprogressing on enzalutamide alone. Pembrolizumab 200 mg intravenous was given every 3 weeks for four doses with enzalutamide. The primary endpoint was prostate-specific antigen (PSA) decline of ≥50%. Secondary endpoints were objective response, PSA progression-free survival (PFS), time to subsequent treatment, and time to death. Baseline tumor biopsies were obtained when feasible, and samples were sequenced and evaluated for the expression of PD-L1, microsatellite instability (MSI), mutational and neoepitope burdens.

resultsFive (18%) of 28 patients had a PSA decline of ≥50%. Three (25%) of 12 patients with measurable disease at baseline achieved an objective response. Of the five responders, two continue with PSA and radiographic response after 39.3 and 37.8 months. For the entire cohort, median follow-up was 37 months, and median PSA PFS time was 3.8 months (95% CI: 2.8 to 9.9 months). Time to subsequent treatment was 7.21 months (95% CI: 5.1 to 11.1 months). Median overall survival for all patients was 21.9 months (95% CI: 14.7 to 28 .4 months), versus 41.7 months (95% CI: 22.16 to not reached (NR)) in the responders. Of the three responders with baseline biopsies, one had MSI high disease with mutations consistent with DNA-repair defects. None had detectable PD-L1 expression.

conclusionsPembrolizumab has activity in mCRPC when added to enzalutamide. Responses were deep and durable and did not require tumor PD-L1 expression or DNA-repair defects. TRIAL REGISTRATION NUMBER: clinicaltrials.gov (NCT02312557).

Indexed as

AgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBenzamidesHumansMaleMiddle AgedNitrilesPhenylthiohydantoinProstatic Neoplasms, Castration-ResistantAntibodies, Monoclonal, HumanizedBenzamidesenzalutamideNitrilespembrolizumabPhenylthiohydantoinbiomarkerscombinationdrug therapyimmunotherapylymphocytesprostatic neoplasmstumortumor-infiltrating

Identifiers

PMID32616555
PMCPMC7333874
OpenAlexW3038718086

What OpenQuestion 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 OpenQuestion graph.