Association of TP53 mutations with response and longer survival under immune checkpoint inhibitors in advanced non-small-cell lung cancer.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Immunological
/ pharmacology
B7-H1 Antigen
/ antagonists & inhibitors
Biomarkers, Tumor
/ genetics
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Female
Follow-Up Studies
High-Throughput Nucleotide Sequencing
Humans
Immunotherapy
/ methods
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Mutation
/ genetics
Neoplasm Staging
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Proto-Oncogene Proteins p21(ras)
/ genetics
Retrospective Studies
Survival Analysis
Tumor Suppressor Protein p53
/ genetics
Immune checkpoint inhibitors
Non-small-cell lung cancer
TP53 mutations
Tumor mutational burden
Journal
Lung cancer (Amsterdam, Netherlands)
ISSN: 1872-8332
Titre abrégé: Lung Cancer
Pays: Ireland
ID NLM: 8800805
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
21
05
2018
revised:
30
03
2019
accepted:
06
04
2019
entrez:
18
5
2019
pubmed:
18
5
2019
medline:
9
4
2020
Statut:
ppublish
Résumé
Tumor mutational burden (TMB) correlates with response to immune checkpoint inhibitors (ICI) in advanced non-small-cell lung cancer (aNSCLC). We hypothesized that TP53 mutations could reflect TMB and be associated with ICI benefit. TP53 mutations were assessed by next-generation sequencing in aNSCLC patients treated with programmed death-1 (PD-1) blockers. Clinical data, tumor programmed death ligand-1 (PD-L1) expression, and KRAS mutational status were collected. The primary endpoint was overall survival (OS). In total, 72 patients (median [interquartile range] age: 61 [33-83] years) were included; 52 (72%) were male; 39 (54%) had performance status 0-1; 53 (74%) had adenocarcinoma; 20 (28%) received first-line ICI, 52 (72%) second line or more. In 65 patients with available data, 36 (55%) expressed PD-L1 in ≥50% of tumor cells, 20 (31%) in 1-49% of cells, and nine (14%) were PD-L1-negative. Non-synonymous TP53 mutations were observed in 41 (57%) and 25 (35%) harbored KRAS-mutated tumors. After a median follow-up of 15.2 months (95% confidence interval [CI] 10.3-17.4 m), the median OS in the TP53-mutated group was 18.1 months (95% CI 6.6-not reached), vs. 8.1 months (95% CI 2.2-14.5, hazard ratio [HR] = 0.48; 95% CI 0.25-0.95, p = 0.04) in the TP53-wild-type group. Median progression-free survival was significantly longer in TP53-mutated patients (4.5 months, 95% CI 2.8-18.1 versus 1.4, 95% CI 1.1-3.5; p = 0.03), although TP53 mutation status failed to significantly influence PFS in the multivariate analysis (p = 0.32). Objective response rate (ORR) was higher in patients with TP53 mutation (51.2% vs. 20.7%; p = 0.01). In multivariate analysis, TP53 mutations independently associated with longer OS (HR = 0.35, 95% CI 0.16-0.77, p = 0.009). TP53-mutated status correlated with immunotherapy OS benefit in aNSCLC.
Identifiants
pubmed: 31097096
pii: S0169-5002(19)30392-7
doi: 10.1016/j.lungcan.2019.04.005
pii:
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
B7-H1 Antigen
0
Biomarkers, Tumor
0
CD274 protein, human
0
KRAS protein, human
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
65-71Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.