Evidence mapPaperPMID 39638782Full record

Trial reportNature communications2024

Integrative multi-omics analysis uncovers tumor-immune-gut axis influencing immunotherapy outcomes in ovarian cancer.

Spencer R Rosario, Mark D Long, Shanmuga Chilakapati, Eduardo Cortes Gomez, Sebastiano Battaglia, Prashant K Singh, Jianmin Wang, Katy Wang, Kristopher Attwood, Suzanne M Hess and 7 more

Registry-linked trialAbstract readClinical Trial, Phase II
In one paragraph

Trial report 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 NCT02853318 (A Phase II Evaluation of Pembrolizumab in Combination With IV Bevacizumab and Oral Metronomic Cyclophosphamide in the Treatment of Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer), which is not on this map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing 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.

NCT02853318 phase2completednot on this map

A Phase II Evaluation of Pembrolizumab in Combination With IV Bevacizumab and Oral Metronomic Cyclophosphamide in the Treatment of Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

TypeinterventionalSponsorRoswell Park Cancer InstituteRan2016 to 2021Enrolled40ConditionsFallopian Tube Clear Cell Adenocarcinoma, Fallopian Tube Endometrioid Adenocarcinoma, Fallopian Tube Mucinous Adenocarcinoma, Fallopian Tube Serous AdenocarcinomaArmsBevacizumab, Cyclophosphamide, Laboratory Biomarker Analysis, Pembrolizumab
3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 1 synthesis or guideline 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

17 authors.

Spencer R Rosario *Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.
Mark D Long *Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.ORCID 0000-0003-1120-8176
Shanmuga ChilakapatiNew England Inflammation and Tissue Protection Institute, Northeastern University, Boston, MA, 02111, USA.
Eduardo Cortes GomezDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.ORCID 0000-0002-0966-6488
Sebastiano BattagliaComputational Biology Office of Translational Research, Janssen Pharmaceuticals, Buffalo, NY, 14263, USA.
Prashant K SinghDepartment of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.
Jianmin WangDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.ORCID 0000-0001-7527-0409
Katy WangDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.
Kristopher AttwoodDepartment of Clinical Research, American College of Radiology, Reston, VA, 20191, USA.
Suzanne M HessDepartment of Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.
A J Robert McGrayDepartment of Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.
Kunle OdunsiDepartment of Obstetrics and Gynecology, University of Chicago Comprehensive Cancer Center, Chicago, IL, 60637, USA.ORCID 0000-0002-4444-7651
Brahm H SegalDepartment of Internal Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.ORCID 0000-0001-5043-7380
Gyorgy ParaghDepartment of Dermatology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.ORCID 0000-0002-6612-9267
Song LiuDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.
Jennifer A WargoDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.ORCID 0000-0003-3438-7576
Emese ZsirosDepartment of Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA. Emese.Zsiros@RoswellPark.org.ORCID 0000-0003-0142-7375

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MARK G FRATTINI · 1985 to 2026
$116.6M
Immuno-Oncology Translation Network: Data Management and Resource-Sharing Center at RPCIU24CA232979 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI HUTSON, ALAN DAVID, LIU, SONG · 2018 to 2024
$8.9M
Transdisciplinary Research in Energetics and Cancer (TREC) Training GrantR25CA203650 · NCI · YALE UNIVERSITY · PI IRWIN, MELINDA L · 2016 to 2025
$2.9M
Acquisition of High Performance Data and Computing Infrastructure to Advance Biomedical ResearchS10OD024973 · OD · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI FURLANI, THOMAS · 2019 to 2019
$1.0M
Director Genomics Shared ResourceR50CA283805 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI Prashant Kumar Singh · 2024 to 2026
$708k
NCI NIH HHS P30 CA016056NCI NIH HHS R25 CA203650NCI NIH HHS R50 CA283805NCI NIH HHS U24 CA232979NIH HHS S10 OD024973U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U24 CA232979-01S5
6 · The paper itself

Abstract

Recurrent ovarian cancer patients, especially those resistant to platinum, lack effective curative treatments. To address this, we conducted a phase 2 clinical trial (NCT02853318) combining pembrolizumab with bevacizumab, to increase T cell infiltration into the tumor, and oral cyclophosphamide, to reduce the number of regulatory T cells. The trial accrued 40 heavily pretreated recurrent ovarian cancer patients. The primary endpoint, progression free survival, was extended to a median of 10.2 months. The secondary endpoints demonstrated an objective response rate of 47.5%, and disease control in 30% of patients for over a year while maintaining a good quality of life. We performed comprehensive molecular, immune, microbiome, and metabolic profiling on samples of trial patients. Here, we show increased T and B cell clusters and distinct microbial patterns with amino acid and lipid metabolism are linked to exceptional clinical responses. This study suggests the immune milieu and host-microbiome can be leveraged to improve antitumor response in future immunotherapy trials.

Indexed as

Antibodies, Monoclonal, HumanizedBevacizumabGastrointestinal MicrobiomeImmunotherapyOvarian NeoplasmsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsCyclophosphamideFemaleHumansMiddle AgedMultiomicsNeoplasm Recurrence, LocalProgression-Free SurvivalQuality of LifeAntibodies, Monoclonal, HumanizedBevacizumabCyclophosphamidepembrolizumab

Identifiers

PMID39638782
PMCPMC11621351

What Socratic holds

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LicenceCC BY
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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 Socratic graph.