Association of TP53 mutations with response and longer survival under immune checkpoint inhibitors in advanced non-small-cell lung cancer
| العنوان: | Association of TP53 mutations with response and longer survival under immune checkpoint inhibitors in advanced non-small-cell lung cancer |
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| المؤلفون: | 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 |
| المساهمون: | 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 |
| المصدر: | Lung Cancer Lung Cancer, Elsevier, 2019, 132, pp.65-71. ⟨10.1016/j.lungcan.2019.04.005⟩ |
| بيانات النشر: | HAL CCSD, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0169-5002 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f87b57ffc47fff47d3b28b188ab317d4Test https://hal.archives-ouvertes.fr/hal-03477631/file/S0169500219303927.pdfTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f87b57ffc47fff47d3b28b188ab317d4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 01695002 |
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