Association of molecular characteristics with survival in advanced non-small cell lung cancer patients treated with checkpoint inhibitors.
FANCA
Immune checkpoint inhibitors
Immunotherapy
Lung cancer
Molecular
Next-generation sequencing (NGS)
PD-L1
TET2
TMB
Journal
Lung cancer (Amsterdam, Netherlands)
ISSN: 1872-8332
Titre abrégé: Lung Cancer
Pays: Ireland
ID NLM: 8800805
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
21
11
2019
revised:
15
05
2020
accepted:
19
05
2020
pubmed:
20
6
2020
medline:
22
6
2021
entrez:
20
6
2020
Statut:
ppublish
Résumé
Immune checkpoint inhibitors (ICIs) have changed the landscape of lung cancer therapy. However significant proportions of patients have primary or acquired resistance to ICIs. Molecular characterization is critical for patient selection and overcoming resistance to checkpoint inhibitors. The purpose of this study is to investigate the molecular characteristics associated with ICIs outcomes in advanced non-small cell lung cancer (NSCLC) patients. All advanced stage NSCLC patients at City of Hope who received ICIs (pembrolizumab, nivolumab, atezolizumab, and durvalumab) were identified retrospectively. Overall survival (OS, from the start of the ICIs), Pathology and information on genomic alterations (GAs) including next-generation sequencing (NGS) data, tumor mutation burden (TMB), and Programmed death-ligand 1 (PD-L1) levels were collected. Chi-square and Fisher's exact test, Log-rank test were used for comparison of demographics, and survival curves respectively. Univariate and multivariate COX proportional hazards model was used for survival analysis. 346 NSCLC patients were identified. Univariate and multivariate analysis found the association of OS with PD-L1 level ≥50% (Hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.06-0.59; P < 0.01), EGFR (HR 7.38; 95% CI, 1.15-47.42; P < 0.05), and TET2 (HR 0.15; 95% CI, 0.03-0.90; P < 0.05). The median OS was not reached [NR] for the 12 patients who had genomic alterations (GAs) in TET2 (12/108, 11%) versus (vs) 11.5 months in TET2 negative patients (98/108, 89%). Interestingly, GAs in TET2 and FANCA were mutually exclusive and patients who had GAs in FANCA gene (6%) had shorter OS (5.5 months vs 14.5 months, Log-rank test, P < 0.05). We described the clinical and molecular features of NSCLC patients treated with ICIs. The association of GAs in TET2 with longer OS and its mutual exclusivity with FANCA GAs were insightful for developing novel therapeutic strategies to improve ICIs outcomes in NSCLC.
Identifiants
pubmed: 32554069
pii: S0169-5002(20)30448-7
doi: 10.1016/j.lungcan.2020.05.025
pmc: PMC8158847
mid: NIHMS1604389
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Nivolumab
31YO63LBSN
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
174-181Subventions
Organisme : NCI NIH HHS
ID : P30 CA033572
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA218545
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA209978
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no competing interests relevant to this work
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