Association of TP53 mutations with response and longer survival under immune checkpoint inhibitors in advanced non-small-cell lung cancer
Autor: | Valérie Gounant, Baptiste Abbar, Claire Danel, Sandra Assoun, Nathalie Théou-Anton, Marina Nguenang, Johan Pluvy, Aurélie Cazes, Antoine Khalil, Céline Namour, Gérard Zalcman, Solenn Brosseau |
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Přispěvatelé: | AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], CCSD, Accord Elsevier |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine Cancer Research Lung Neoplasms [SDV]Life Sciences [q-bio] Programmed Cell Death 1 Receptor medicine.disease_cause Gastroenterology B7-H1 Antigen Antineoplastic Agents Immunological 0302 clinical medicine Interquartile range Carcinoma Non-Small-Cell Lung Clinical endpoint Aged 80 and over TP53 mutations Hazard ratio High-Throughput Nucleotide Sequencing Middle Aged 3. Good health [SDV] Life Sciences [q-bio] Oncology 030220 oncology & carcinogenesis Adenocarcinoma Female Immunotherapy KRAS Adult Pulmonary and Respiratory Medicine medicine.medical_specialty Proto-Oncogene Proteins p21(ras) 03 medical and health sciences Immune checkpoint inhibitors Internal medicine Biomarkers Tumor medicine Humans Lung cancer Aged Neoplasm Staging Retrospective Studies Performance status business.industry medicine.disease Survival Analysis Confidence interval Tumor mutational burden 030104 developmental biology Mutation Tumor Suppressor Protein p53 business Non-small-cell lung cancer Follow-Up Studies |
Zdroj: | Lung Cancer Lung Cancer, Elsevier, 2019, 132, pp.65-71. ⟨10.1016/j.lungcan.2019.04.005⟩ |
ISSN: | 0169-5002 |
Popis: | 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. |
Databáze: | OpenAIRE |
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