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
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
Externí odkaz: