Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial.

Antibodies, Monoclonal, Humanized / therapeutic use Antineoplastic Agents, Immunological / metabolism Biomarkers, Tumor / metabolism Humans Mutation Urinary Bladder Neoplasms / drug therapy

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
12 2021
Historique:
received: 18 12 2020
accepted: 13 10 2021
pubmed: 12 12 2021
medline: 22 2 2022
entrez: 11 12 2021
Statut: ppublish

Résumé

In a recent phase 3 randomized trial of 700 patients with advanced urothelial cancer (JAVELIN Bladder 100; NCT02603432 ), avelumab/best supportive care (BSC) significantly prolonged overall survival relative to BSC alone as maintenance therapy after first-line chemotherapy. Exploratory biomarker analyses were performed to identify biological pathways that might affect survival benefit. Tumor molecular profiling by immunohistochemistry, whole-exome sequencing and whole-transcriptome sequencing revealed that avelumab survival benefit was positively associated with PD-L1 expression by tumor cells, tumor mutational burden, APOBEC mutation signatures, expression of genes underlying innate and adaptive immune activity and the number of alleles encoding high-affinity variants of activating Fcγ receptors. Pathways connected to tissue growth and angiogenesis might have been associated with reduced survival benefit. Individual biomarkers did not comprehensively identify patients who could benefit from therapy; however, multi-parameter models incorporating genomic alteration, immune responses and tumor growth showed promising predictive utility. These results characterize the complex biologic pathways underlying survival benefit from immune checkpoint inhibition in advanced urothelial cancer and suggest that multiple biomarkers might be needed to identify patients who would benefit from treatment.

Identifiants

DOI: 10.1038/s41591-021-01579-0 PMID: 34893775
pubmed: 34893775
doi: 10.1038/s41591-021-01579-0
pii: 10.1038/s41591-021-01579-0
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
Antineoplastic Agents, Immunological 0
Biomarkers, Tumor 0
avelumab KXG2PJ551I

Banques de données

figshare
['0.25454/pfizer.figshare.14866920']
ClinicalTrials.gov
['NCT02603432']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2200-2211

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Thomas Powles (T)

Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St. Bartholomew's Hospital, London, UK. thomas.powles1@nhs.net.
ORCID: 0000-0001-7760-4724

Srikala S Sridhar (SS)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Yohann Loriot (Y)

Gustave Roussy, INSERMU981, Université Paris-Saclay, Villejuif, France.

Joaquim Bellmunt (J)

Department of Medical Oncology, Beth Israel Deaconess Medical Center and IMIM-PSMAR Lab, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0003-2328-3421

Xinmeng Jasmine Mu (XJ)

Computational Biology, Oncology Research and Development, Pfizer, La Jolla, CA, USA.

Keith A Ching (KA)

Computational Biology, Oncology Research and Development, Pfizer, La Jolla, CA, USA.

Jie Pu (J)

Statistics, Global Biometrics and Data Management, Pfizer, La Jolla, CA, USA.

Cora N Sternberg (CN)

Englander Institute for Precision Medicine, Weill Cornell Medicine, Hematology/Oncology, Meyer Cancer Center, New York, NY, USA.

Daniel P Petrylak (DP)

Yale Cancer Center, New Haven, CT, USA.

Rosa Tambaro (R)

Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS Fondazione Giovanni Pascale, Naples, Italy.

Louis M Dourthe (LM)

Service d'Oncologie Médicale, Clinique St Anne, Strasbourg, France.

Carlos Alvarez-Fernandez (C)

Department of Medical Oncology, Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain.
ORCID: 0000-0002-2500-074X

Maureen Aarts (M)

Department of Medical Oncology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands.

Alessandra di Pietro (A)

Pfizer Italia srl, Milano, Italy.

Petros Grivas (P)

Department of Medicine, Division of Medical Oncology, University of Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, Seattle, WA, USA.
ORCID: 0000-0003-3965-3394

Craig B Davis (CB)

Translational Oncology, Pfizer, La Jolla, CA, USA. craig.davis@pfizer.com.
ORCID: 0000-0002-1703-451X

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Avelumab maintenance in advanced urothelial...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Antinéoplasiques immunologiques › Avelumab maintenance in advanced urothelial...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Avelumab maintenance in advanced urothelial...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Avelumab maintenance in advanced urothelial...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Avelumab maintenance in advanced urothelial...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Tumeurs urologiques › Tumeurs de la vessie urinaire › Avelumab maintenance in advanced urothelial...