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The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.

Association of TP53 mutations with response and longer survival under immune checkpoint inhibitors in advanced non-small-cell lung cancer

Open access
Assoun, Sandra, Theou-Anton, Nathalie, Nguenang, Marina, Cazes, Aurélie, Danel, Claire, Abbar, Baptiste, Pluvy, Johan, Gounant, Valérie, Khalil, Antoine, Namour, Céline, Brosseau, Solenn, Zalcman, Gérard·2019·Lung Cancer
DOI 10.1016/j.lungcan.2019.04.005
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Abstract

INTRODUCTION: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: TP53-mutated status correlated with immunotherapy OS benefit in aNSCLC.

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Metadata

Authors
Assoun, S., Theou-Anton, N., Nguenang, M., Cazes, A., Danel, C., Abbar, B., Pluvy, J., Gounant, V., Khalil, A., Namour, C., Brosseau, S., & Zalcman, G.
Venue
Lung Cancer
Publisher
Elsevier BV
Published
2019-06
Volume
132
Pages
65-71
ISSN
0169-5002 (ISSN-L)
DOI
10.1016/j.lungcan.2019.04.005
OpenAlex
W2936661866
Cited by
172
References
15
FWCI
7.44
Type
journal article
Language
en
Open access
hybrid

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Assoun, S., Theou-Anton, N., Nguenang, M., Cazes, A., Danel, C., Abbar, B., Pluvy, J., Gounant, V., Khalil, A., Namour, C., Brosseau, S., & Zalcman, G. (2019). Association of TP53 mutations with response and longer survival under immune checkpoint inhibitors in advanced non-small-cell lung cancer. Lung Cancer. https://doi.org/10.1016/j.lungcan.2019.04.005

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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