Relationship between PD-L1 expression and outcome in EGFR-mutant lung cancer patients treated with EGFR tyrosine kinase inhibitors.

Aged B7-H1 Antigen / genetics Carcinoma, Non-Small-Cell Lung / drug therapy Drug Resistance, Neoplasm / genetics ErbB Receptors / genetics Female Humans Lung Neoplasms / drug therapy Male Mutation Protein Kinase Inhibitors / therapeutic use Retrospective Studies
De novo resistance EGFR mutated NSCLC PD-L1 Programmed death ligand 1

Journal

Lung cancer (Amsterdam, Netherlands)
ISSN: 1872-8332
Titre abrégé: Lung Cancer
Pays: Ireland
ID NLM: 8800805

Informations de publication

Date de publication:
05 2021
Historique:
received: 17 10 2020
revised: 24 02 2021
accepted: 03 03 2021
pubmed: 16 3 2021
medline: 22 6 2021
entrez: 15 3 2021
Statut: ppublish

Résumé

Predictive biomarkers for poor response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is an area of ongoing research. This multicentre retrospective study sought to determine the impact of programmed death-ligand 1 (PD-L1) tumour proportional score (TPS) on outcome in EGFR TKI treated patients. Patients with Stage IIIB/IV lung adenocarcinoma harbouring a sensitising EGFR mutation treated with first-line TKI at five metropolitan hospitals were included. PD-L1 TPS was determined using the Ventana anti-PD-L1 (SP263) assay. High PD-L1 expression was defined as TPS ≥ 50 %. Determinants of progression and survival hazards were modelled using Cox regression. A total of 186 patients were included. Mean age was 67 years, 66 % were female and 54 % were Asian. Patients with high PD-L1 expression (n = 23; 12 %) had significantly shorter progression free survival (6.6 vs 13.0 months, hazard ratio (HR) 2.6 95 % CI 1.6-4.2, p < 0.0001) and overall survival (11.5 vs 32.9 months, HR 3.3, 95 % CI 1.9-5.7, p < 0.0001) compared to patients with PD-L1 low/negative tumours. This remained significant in multivariate analyses. High PD-L1 in post-TKI progression biopsies was not associated with poorer survival. In this large, real-world cohort of EGFR-mutant lung adenocarcinoma patients, high PD-L1 expression was associated with early resistance to 1st generation EGFR TKIs and shorter survival, regardless of ethnicity.

Identifiants

DOI: 10.1016/j.lungcan.2021.03.004 PMID: 33721613
pubmed: 33721613
pii: S0169-5002(21)00100-8
doi: 10.1016/j.lungcan.2021.03.004
pii:
doi:

Substances chimiques

B7-H1 Antigen 0
Protein Kinase Inhibitors 0
EGFR protein, human EC 2.7.10.1
ErbB Receptors EC 2.7.10.1

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

28-33

Informations de copyright

Copyright © 2021 Elsevier B.V. All rights reserved.

Auteurs

Jia Liu (J)

Crown Princess Mary Cancer Centre, Westmead, NSW, Australia; Blacktown Hospital, Blacktown, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Children's Medical Research Institute, Westmead, NSW, Australia.

Malinda Itchins (M)

Northern Clinical School, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia.

Adnan Nagrial (A)

Crown Princess Mary Cancer Centre, Westmead, NSW, Australia; Blacktown Hospital, Blacktown, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia.

Wendy A Cooper (WA)

Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, NSW Health Pathology, NSW, Australia; Sydney School of Medicine, Western Sydney University, NSW, Australia.

Madhawa De Silva (M)

Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia.

Megan Barnet (M)

Kinghorn Cancer Centre, Darlinghurst, NSW, Australia; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.

Winny Varikatt (W)

Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Tissue Pathology and Diagnostic Oncology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia.

Vanathi Sivasubramaniam (V)

Sydpath, St Vincent's Hospital, Darlinghurst, NSW, Australia.

Alexander Davis (A)

Chris O'Brien Lifehouse, Camperdown, NSW, Australia.

Anthony J Gill (AJ)

Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Northern Clinical School, University of Sydney, Sydney, NSW, Australia; NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia.

Prunella Blinman (P)

Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Concord Repatriation General Hospital, Concord, NSW, Australia.

Kenneth Lee (K)

Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Department of Anatomical Pathology, NSW Health Pathology, Concord Repatriation General Hospital, Sydney, NSW, Australia.

Rina Hui (R)

Crown Princess Mary Cancer Centre, Westmead, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia.

Bo Gao (B)

Crown Princess Mary Cancer Centre, Westmead, NSW, Australia; Blacktown Hospital, Blacktown, NSW, Australia.

Nick Pavlakis (N)

Northern Clinical School, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia.

Stephen Clarke (S)

Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Northern Clinical School, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia.

Jenny Lee (J)

Chris O'Brien Lifehouse, Camperdown, NSW, Australia.

Michael Boyer (M)

Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Chris O'Brien Lifehouse, Camperdown, NSW, Australia.

Steven Kao (S)

Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Chris O'Brien Lifehouse, Camperdown, NSW, Australia. Electronic address: steven.kao@lh.org.au.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Relationship between PD-L1 expression and...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Antigènes B7 › Antigène CD274 › Relationship between PD-L1 expression and...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Tumeurs des bronches › Carcinome bronchogénique › Carcinome pulmonaire non à petites cellules › Relationship between PD-L1 expression and...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Résistance aux médicaments antinéoplasiques › Relationship between PD-L1 expression and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur facteur croissance › Récepteurs ErbB › Relationship between PD-L1 expression and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Relationship between PD-L1 expression and...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Relationship between PD-L1 expression and...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Relationship between PD-L1 expression and...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de protéines kinases › Relationship between PD-L1 expression and...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études rétrospectives › Relationship between PD-L1 expression and...