PDL1 high expression without TP53, KEAP1 and EPHA5 mutations could better predict survival for patients with NSCLC receiving atezolizumab.
Antibodies, Monoclonal, Humanized
B7-H1 Antigen
/ metabolism
Carcinoma, Non-Small-Cell Lung
/ drug therapy
DNA Helicases
Humans
Kelch-Like ECH-Associated Protein 1
/ genetics
Lung Neoplasms
/ drug therapy
Mutation
NF-E2-Related Factor 2
/ genetics
Nuclear Proteins
Receptor, EphA5
Transcription Factors
Tumor Suppressor Protein p53
/ genetics
Atezolizumab
EPHA5
KEAP1
NSCLC
PDL1
TP53
Journal
Lung cancer (Amsterdam, Netherlands)
ISSN: 1872-8332
Titre abrégé: Lung Cancer
Pays: Ireland
ID NLM: 8800805
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
23
09
2020
revised:
21
10
2020
accepted:
10
11
2020
pubmed:
29
11
2020
medline:
28
5
2021
entrez:
28
11
2020
Statut:
ppublish
Résumé
Non-small cell lung cancer (NSCLC) patients with high expression of PDL1 are more likely to benefit from atezolizumab. There are no relevant research focusing on the relationship between the PDL1 expression and clinical variables and gene mutation types among NSCLC patients. NSCLC patients with confirmed PDL1 expression and gene mutation information from OAK study were included in our study. Logistic regression proportional model was applied to analyze the risk factors on PDL1 high expression. The biomarker evaluable population (BEP) was screened to analyze the gene mutation informaion among these patients. High frequency gene mutations were screened based on different PDL1 expressions. Moreover, the log rank test was applied to analyze the overall survival (OS) difference based on different gene mutation types. A total of 838 patients with NSCLC were included in our study. White patients are more likely to have PDL1 ≥ 1% (P = 0.004). ERBB4, EP300, PREX2, SLIT2, EPHB1 and IGF2R mutations were high frequency mutations in patients with high PDL1 expression, and the patients with EGFR, SMARCA4, EPHA5, FAT1, STK11, TET2 mutations were more likely to be seen in negative PDL1 expression group. Worse survival could be found in patients with KEAP1 (P < 0.001), TP53 (P = 0.004) and EPHA5 (P = 0.013) mutations who received atezolizumab compared with those who had none of these gene mutations. Importantly, for PDL1 high patients without KEAP1, EPHA5, TP53 mutations receiving atezolizumab, they all showed relatively longer median survival with 22.47, 22.18 and 23.33 months, respectively (all, P < 0.01). Different high frequency gene mutations could be found between the patients with high and negative PDL1. PDL1 expression combined with specific gene mutation may better predict the survival for patients receiving atezolizumab.
Sections du résumé
BACKGROUND
Non-small cell lung cancer (NSCLC) patients with high expression of PDL1 are more likely to benefit from atezolizumab. There are no relevant research focusing on the relationship between the PDL1 expression and clinical variables and gene mutation types among NSCLC patients.
METHODS
NSCLC patients with confirmed PDL1 expression and gene mutation information from OAK study were included in our study. Logistic regression proportional model was applied to analyze the risk factors on PDL1 high expression. The biomarker evaluable population (BEP) was screened to analyze the gene mutation informaion among these patients. High frequency gene mutations were screened based on different PDL1 expressions. Moreover, the log rank test was applied to analyze the overall survival (OS) difference based on different gene mutation types.
RESULTS
A total of 838 patients with NSCLC were included in our study. White patients are more likely to have PDL1 ≥ 1% (P = 0.004). ERBB4, EP300, PREX2, SLIT2, EPHB1 and IGF2R mutations were high frequency mutations in patients with high PDL1 expression, and the patients with EGFR, SMARCA4, EPHA5, FAT1, STK11, TET2 mutations were more likely to be seen in negative PDL1 expression group. Worse survival could be found in patients with KEAP1 (P < 0.001), TP53 (P = 0.004) and EPHA5 (P = 0.013) mutations who received atezolizumab compared with those who had none of these gene mutations. Importantly, for PDL1 high patients without KEAP1, EPHA5, TP53 mutations receiving atezolizumab, they all showed relatively longer median survival with 22.47, 22.18 and 23.33 months, respectively (all, P < 0.01).
CONCLUSIONS
Different high frequency gene mutations could be found between the patients with high and negative PDL1. PDL1 expression combined with specific gene mutation may better predict the survival for patients receiving atezolizumab.
Identifiants
pubmed: 33246647
pii: S0169-5002(20)30681-4
doi: 10.1016/j.lungcan.2020.11.006
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
B7-H1 Antigen
0
CD274 protein, human
0
KEAP1 protein, human
0
Kelch-Like ECH-Associated Protein 1
0
NF-E2-Related Factor 2
0
Nuclear Proteins
0
TP53 protein, human
0
Transcription Factors
0
Tumor Suppressor Protein p53
0
atezolizumab
52CMI0WC3Y
EPHA5 protein, human
EC 2.7.10.1
Receptor, EphA5
EC 2.7.10.1
SMARCA4 protein, human
EC 3.6.1.-
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
76-83Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.