Evidence map›Paper›PMID 34750557›Full record

Trial reportNature medicine2021

Durvalumab with platinum-pemetrexed for unresectable pleural mesothelioma: survival, genomic and immunologic analyses from the phase 2 PrE0505 trial.

Patrick M Forde, Valsamo Anagnostou, Zhuoxin Sun, Suzanne E Dahlberg, Hedy L Kindler, Noushin Niknafs, Thomas Purcell, Rafael Santana-Davila, Arkadiusz Z Dudek, Hossein Borghaei and 17 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02899195 (Open Label, Phase II Study of Anti - Programmed Death - Ligand 1 Antibody, Durvalumab), which is not on this map. Cited by 82 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 1 pooled it
12.8field-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.

NCT02899195 phase2completednot on this map

Open Label, Phase II Study of Anti - Programmed Death - Ligand 1 Antibody, Durvalumab (MEDI4736), in Combination With Chemotherapy for the First-Line Treatment of Unresectable Mesothelioma

TypeinterventionalSponsorPrECOG, LLC.Ran2017 to 2023Enrolled55ConditionsMesothelioma, Pleural MesotheliomaArmsDurvalumab
3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.

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22 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

27 authors at 9 institutions in 1 country.

Patrick M Forde *The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. pforde1@jhmi.edu.ORCID http://orcid.org/0000-0001-6925-6344
Valsamo Anagnostou *The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. vanagno1@jhmi.edu.ORCID http://orcid.org/0000-0001-9480-3047
Zhuoxin Sun *ECOG-ACRIN Biostatistics Center, Boston, MA, USA.
Suzanne E DahlbergBoston Children's Hospital, Boston, MA, USA.
Hedy L KindlerUniversity of Chicago Medicine, Chicago, IL, USA.
Noushin NiknafsThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Thomas PurcellUniversity of Washington School of Medicine & Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Rafael Santana-DavilaUniversity of Washington School of Medicine & Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Arkadiusz Z DudekMetro-Minnesota Community Oncology Research Consortium, St. Louis Park, MN, USA.
Hossein BorghaeiFox Chase Cancer Center, Philadelphia, PA, USA.
Mara LanisThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Zineb BelcaidThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kellie N SmithThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Archana BalanThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
James R WhiteThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Christopher CherryThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
I K Ashok SivakumarInstitute for Computational Medicine, Johns Hopkins University, Baltimore, MD, USA.
Xiaoshan M ShaoInstitute for Computational Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-3190-2288
Hok Yee ChanThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Dipika SinghThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sampriti ThapaThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Peter B IlleiThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Drew M PardollThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rachel KarchinThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-5069-1239
Victor E VelculescuThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-1195-438X
Julie R BrahmerThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Suresh S RamalingamDepartment of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-0757-3106
Johns Hopkins University · USBloomberg (United States) · USUniversity of Washington · USBoston Children's Hospital · USECOG-ACRIN Cancer Research Group · USEmory University · USFox Chase Cancer Center · USMetro-Minnesota Community Oncology Research Consortium · USUniversity of Chicago · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN KEITH MEEKER · 1985 to 2026
$208.6M
ECOG-ACRIN Thoracic Malignancies Integrated Translational Science CenterUG1CA233259 · NCI · EMORY UNIVERSITY · PI CARBONE, DAVID P., LEAL, TICIANA · 2019 to 2025
$5.1M
Large-Scale Genetic Analyses of Human CancerR01CA121113 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANAGNOSTOU, VALSAMO, VELCULESCU, VICTOR E. · 2006 to 2022
$4.3M
Immunogenomic determinants of response and resistance to neoadjuvant anti-PD-1 in resectable NSCLCR37CA251447 · NCI · JOHNS HOPKINS UNIVERSITY · PI Kellie Nicole Smith · 2021 to 2026
$2.2M
NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA121113NCI NIH HHS R37 CA251447NCI NIH HHS UG1 CA233259
6 · The paper itself

Abstract

Mesothelioma is a rare and fatal cancer with limited therapeutic options until the recent approval of combination immune checkpoint blockade. Here we report the results of the phase 2 PrE0505 trial ( NCT02899195 ) of the anti-PD-L1 antibody durvalumab plus platinum-pemetrexed chemotherapy for 55 patients with previously untreated, unresectable pleural mesothelioma. The primary endpoint was overall survival compared to historical control with cisplatin and pemetrexed chemotherapy; secondary and exploratory endpoints included safety, progression-free survival and biomarkers of response. The combination of durvalumab with chemotherapy met the pre-specified primary endpoint, reaching a median survival of 20.4 months versus 12.1 months with historical control. Treatment-emergent adverse events were consistent with known side effects of chemotherapy, and all adverse events due to immunotherapy were grade 2 or lower. Integrated genomic and immune cell repertoire analyses revealed that a higher immunogenic mutation burden coupled with a more diverse T cell repertoire was linked to favorable clinical outcome. Structural genome-wide analyses showed a higher degree of genomic instability in responding tumors of epithelioid histology. Patients with germline alterations in cancer predisposing genes, especially those involved in DNA repair, were more likely to achieve long-term survival. Our findings indicate that concurrent durvalumab with platinum-based chemotherapy has promising clinical activity and that responses are driven by the complex genomic background of malignant pleural mesothelioma.

Indexed as

AdultAgedAged, 80 and overAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCisplatinDNA RepairFemaleGenetic Predisposition to DiseaseGerm-Line MutationHumansMaleMesothelioma, MalignantMiddle AgedAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalBAP1 protein, humanCarboplatinCisplatindurvalumabNucleic Acid Synthesis InhibitorsPemetrexedTumor Suppressor ProteinsUbiquitin Thiolesterase

Identifiers

PMID34750557
PMCPMC8604731
OpenAlexW3211455418

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.