Evidence map›Paper›PMID 30742122›Full record

Trial reportNature medicine2019

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Timothy F Cloughesy, Aaron Y Mochizuki, Joey R Orpilla, Willy Hugo, Alexander H Lee, Tom B Davidson, Anthony C Wang, Benjamin M Ellingson, Julie A Rytlewski, Catherine M Sanders and 20 more

2 registry-linked trialsAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 924 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
924citing papers in PubMed, 6 pooled it
100.8field-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.

NCT05235737 phase4unknown statusnot on this mapstarted 2022, after this paper: background citation

A Single Center, Open-Label, Randomized Study to Evaluate the Safety and Efficacy of Neoadjuvant and Adjuvant Pembrolizumab on Top of Standard Chemo-Radiotherapy (Stupp Protocol) in Treatment of Patients With Newly Diagnosed Glioblastoma Multiforme (GBM).

TypeinterventionalSponsorMedical University of SilesiaRan2022 to 2026Enrolled36ConditionsNewly Diagnosed GlioblastomaArmsPembrolizumab
NCT05459415 naactive not recruitingnot on this mapstarted 2022, after this paper: background citation

Reducing Excision Margins After Neoadjuvant Chemoimmunotherapy for HPV Negative Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma (REMATCH)

TypeinterventionalSponsorUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyRan2022 to 2027Enrolled54ConditionsSquamous Cell Carcinoma of Head and Neck, Neoadjuvant Therapy, Resection MarginArmsReducing Excision Margins
3 · Its place in the literature

Who cites it

924 citing papers in PubMed, 6 syntheses or guidelines pooled it, 1,356 citations in OpenAlex.

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  5. Anti-PD-1 and anti-PD-L1 antibodies for glioma.The Cochrane database of systematic reviews · 2025
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  18. Immunotherapy for Glioma: A compartmental framework for resistance and rational combination design.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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  20. Crosslink Between Neuroinflammation and Oxidative/Nitrosative Status in the Glioblastoma Tumor Microenvironment: Prognostic and Theranostic Impact.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026
    Article

864 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 8 institutions in 1 country.

Timothy F CloughesyDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. tcloughesy@mednet.ucla.edu.ORCID http://orcid.org/0000-0002-8656-7483
Aaron Y MochizukiDivision of Hematology/Oncology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-1073-916X
Joey R OrpillaDepartment of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-6679-9463
Willy HugoDivision of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-1426-7190
Alexander H LeeDepartment of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-4583-0740
Tom B DavidsonJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Anthony C WangDepartment of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Benjamin M EllingsonJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Julie A RytlewskiAdaptive Biotechnologies, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-5244-6790
Catherine M SandersAdaptive Biotechnologies, Seattle, WA, USA.
Eric S KawaguchiDepartment of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA.
Lin DuDepartment of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA.
Gang LiJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
William H YongDepartment of Pathology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Sarah C GaffeyCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Adam L CohenDepartment of Neurosurgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.ORCID http://orcid.org/0000-0002-8541-2287
Ingo K MellinghoffDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Eudocia Q LeeCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
David A ReardonCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Barbara J O'BrienDepartment of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nicholas A ButowskiDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Phioanh L NghiemphuDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Jennifer L ClarkeDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Isabel C Arrillaga-RomanyDepartment of Neurology, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Howard ColmanDepartment of Neurosurgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Thomas J KaleyDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
John F de GrootDepartment of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Linda M LiauJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Patrick Y WenCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Robert M PrinsDepartment of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. rprins@mednet.ucla.edu.ORCID http://orcid.org/0000-0002-6282-6583
University of California, Los Angeles · USCenter for Neuro-Oncology · USAdaptive Biotechnologies (United States) · USMemorial Sloan Kettering Cancer Center · USThe University of Texas MD Anderson Cancer Center · USUniversity of California, San Francisco · USUniversity of Utah · USMassachusetts General Hospital · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
Center for Clinical and Translational Sciences (CCTS)UL1TR000371 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2012 to 2016
$13.4M
UCLA Tumor Immunology Training ProgramT32CA009120 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Steven M. Dubinett, MICHAEL A TEITELL · 1985 to 2026
$10.3M
Immunotherapeutic targeting of the Glioblastoma MutanomeR21CA186004 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LARGAESPADA, DAVID ANDREW, PRINS, ROBERT M · 2015 to 2016
$380k
NCATS NIH HHS UL1 TR000371NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA211015NCI NIH HHS R21 CA186004NCI NIH HHS T32 CA009120
6 · The paper itself

Abstract

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor.

Indexed as

AdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalBrain NeoplasmsChemotherapy, AdjuvantFemaleGlioblastomaHumansMaleMiddle AgedNeoadjuvant TherapyNeoplasm Recurrence, LocalNeurosurgical ProceduresProgrammed Cell Death 1 ReceptorSurvival RateAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalpembrolizumabProgrammed Cell Death 1 Receptor

Identifiers

PMID30742122
PMCPMC6408961
OpenAlexW2911752971

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.