Evidence map›Paper›PMID 39737895›Full record

ArticleNature communications2024

Neoadjuvant anti-PD1 immunotherapy for surgically accessible recurrent glioblastoma: clinical and molecular outcomes of a stage 2 single-arm expansion cohort.

J Ricardo McFaline-Figueroa, Lu Sun, Gilbert C Youssef, Raymond Huang, Gang Li, Jiyoon Kim, Eudocia Q Lee, Lakshmi Nayak, Ugonma Chukwueke, Rameen Beroukhim and 26 more

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02852655 (A Pilot Surgical Trial To Evaluate Early Immunologic Pharmacodynamic Parameters For The PD-1 Checkpoint Inhibitor, Pembrolizumab), which is not on this map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 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.

NCT02852655 phase1active not recruitingnot on this map

A Pilot Surgical Trial To Evaluate Early Immunologic Pharmacodynamic Parameters For The PD-1 Checkpoint Inhibitor, Pembrolizumab (MK-3475), In Patients With Surgically Accessible Recurrent/Progressive Glioblastoma

TypeinterventionalSponsorDana-Farber Cancer InstituteRan2016 to 2026Enrolled60ConditionsBrain CancerArmsMK-3475
3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  5. 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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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

36 authors.

J Ricardo McFaline-Figueroa *Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-6670-1841
Lu Sun *Department of Neurosurgery, University of California Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-6592-1156
Gilbert C YoussefCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Raymond HuangDepartment of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Gang LiDepartment of Biostatistics, Jonathan and Karin Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA.
Jiyoon KimDepartment of Biostatistics, Jonathan and Karin Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA.
Eudocia Q LeeCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Lakshmi NayakCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Ugonma ChukwuekeCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Rameen BeroukhimCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0001-6303-3609
Tracy T BatchelorCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
E Antonio ChioccaDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-5183-1670
Richard G EversonDepartment of Neurosurgery, University of California Los Angeles, Los Angeles, CA, USA.ORCID 0000-0003-2809-3061
Lisa DohertyCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Jennifer StefanikCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Kathryn PartridgeCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Amanda SpearmanCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Alexa MyersCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Catharina WestergaardCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Alyssa RussCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-6353-139X
Maria LavalleeCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Anna SmokovichCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Corey LaForest-RoysCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Rachel Garcia FoxCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Christine McCluskeyCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Wenya Linda BiDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Omar ArnaoutDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
PierPaolo PeruzziDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-5034-2963
G Rees CosgroveDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Keith L LigonDivision of Neuropathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-7733-600X
Isabel Arrillaga-RomanyDivision of Neuro-Oncology, Mass General Cancer Center, Harvard Medical School, Boston, MA, USA.
Jennifer L ClarkeDepartments of Neurology and Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-8054-7342
David A ReardonCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0001-6674-0157
Timothy F CloughesyJonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-8656-7483
Robert M PrinsDepartment of Neurosurgery, University of California Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-6282-6583
Patrick Y WenCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Patrick_Wen@dfci.harvard.edu.ORCID 0000-0002-0774-7700

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
Neoadjuvant checkpoint blockade for recurrent glioblastomaR01CA267726 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert M Prins · 2022 to 2026
$2.4M
NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA267726
6 · The paper itself

Abstract

Glioblastoma is immunologically "cold" and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655). Neoadjuvant pembrolizumab was associated with suppression of cell cycle/cancer proliferation genes and upregulation of T-cell/interferon-related gene expression. This signature was unique to patients treated with neoadjuvant pembrolizumab and was an independent positive risk factor for survival. Our results demonstrate a clear pharmacodynamic effect of anti-PD1 therapy in glioblastoma and identify pathways that may mediate resistance. However, we did not confirm a survival benefit to neoadjuvant pembrolizumab in recurrent glioblastoma and our secondary endpoint of PFS-6 was 19.5% (95% CI: 9.29-41.2%) for the pooled neoadjuvant cohorts. Our new data suggests some patients may exhibit innate resistance to pre-surgical ICI and require other concomitant therapies to sensitize effectively.

Indexed as

Antibodies, Monoclonal, HumanizedBrain NeoplasmsGlioblastomaImmune Checkpoint InhibitorsNeoadjuvant TherapyNeoplasm Recurrence, LocalProgrammed Cell Death 1 ReceptorAdultAgedCohort StudiesFemaleGene Expression Regulation, NeoplasticHumansImmunotherapyMaleMiddle AgedAntibodies, Monoclonal, HumanizedImmune Checkpoint InhibitorsPDCD1 protein, humanpembrolizumabProgrammed Cell Death 1 Receptor

Identifiers

PMID39737895
PMCPMC11685579

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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.