Clinical and molecular characteristics associated with high PD-L1 expression in EGFR-mutated lung adenocarcinoma.
Autor: | Slomka J; Thoracic Oncology Unit, Pneumology, Cochin Hospital AP-HP Paris, Paris, France., Berthou H; Thoracic Oncology, Georges-Pompidou European Hospital, AP-HP Paris, Paris, France., Mansuet-Lupo A; Pathology Department, Cochin Hospital, AP-HP Paris, Paris, France.; Team 'Cancer, Immune Control and Escape' Inserm U1138, Cordeliers Research Centre, Paris, France.; Faculty of Medicine, Université Paris Cité, Paris, France., Blons H; Faculty of Medicine, Université Paris Cité, Paris, France.; Biochemistry Department, Molecular Oncology and Pharmacogenetics Unit, Georges-Pompidou European Hospital, AP-HP Paris, Paris, France.; Immunotherapy and Antiangiogenic Treatment in Cancerology, INSERM U970, Université Paris-Cité, Paris, France., Fabre E; Thoracic Oncology, Georges-Pompidou European Hospital, AP-HP Paris, Paris, France., Lerner I; Faculty of Medicine, Université Paris Cité, Paris, France.; Informatics and Practice Evaluation, Georges-Pompidou European Hospital, AP-HP Paris, Paris, France., Rance B; Faculty of Medicine, Université Paris Cité, Paris, France.; Informatics and Practice Evaluation, Georges-Pompidou European Hospital, AP-HP Paris, Paris, France., Alifano M; Faculty of Medicine, Université Paris Cité, Paris, France.; Thoracic and Cardiovascular Surgery, Cochin Hospital, AP-HP Paris, Paris, France., Chapron J; Thoracic Oncology Unit, Pneumology, Cochin Hospital AP-HP Paris, Paris, France., Birsen G; Thoracic Oncology Unit, Pneumology, Cochin Hospital AP-HP Paris, Paris, France., Gibault L; Pathology Department, Georges-Pompidou European Hospital, AP-HP Paris, Paris, France., Arrondeau J; Medical Oncology, Cochin Hospital, AP-HP Paris, Paris, France., Leroy K; Team 'Cancer, Immune Control and Escape' Inserm U1138, Cordeliers Research Centre, Paris, France.; Faculty of Medicine, Université Paris Cité, Paris, France.; Biochemistry Department, Molecular Oncology and Pharmacogenetics Unit, Georges-Pompidou European Hospital, AP-HP Paris, Paris, France., Wislez M; Thoracic Oncology Unit, Pneumology, Cochin Hospital AP-HP Paris, Paris, France.; Team 'Cancer, Immune Control and Escape' Inserm U1138, Cordeliers Research Centre, Paris, France.; Faculty of Medicine, Université Paris Cité, Paris, France. |
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Jazyk: | angličtina |
Zdroj: | PloS one [PLoS One] 2024 Nov 07; Vol. 19 (11), pp. e0307161. Date of Electronic Publication: 2024 Nov 07 (Print Publication: 2024). |
DOI: | 10.1371/journal.pone.0307161 |
Abstrakt: | Objective: Recent evidence suggests that elevated levels of PD-L1 expression may be linked to early resistance to TKI and reduced survival in NSCLC with EGFR mutations. This study aimed to characterize the clinical and molecular features of EGFR-mutated lung adenocarcinomas and determine the prognostic significance associated with high PD-L1 expression. Materials and Methods: We conducted a retrospective chart review of 103 consecutive patients with advanced EGFR-mutated NSCLC, who received treatment between 01/01/2016 and 30/12/2020, at our institution. Results: Among the tumors, 17% (n = 18) exhibited high PD-L1 expression (≥50% tumor proportion score), which was associated with a lower prevalence of common EGFR mutations (56% vs. 82%, p = 0.03) and a higher frequency of complex EGFR mutations (28% vs. 7%, p = 0.02). Univariate analysis did not reveal any significant differences in first-line response, progression-free survival, or overall survival between the PD-L1 ≥50% and <50% groups. However, multivariate analysis demonstrated that PD-L1 ≥50% was independently associated with shorter survival (HR = 2.57; 95%CI[1.20-5.55]; p = 0.02), along with male gender (HR = 2.77; 95%CI[1.54-4.19]; p<0.005), presence of liver metastases (HR = 5.80; 95%CI[2.86-11.75]; p<0.005) or brain metastases (HR = 1.99; 95%CI[1.13-3.52]; p = 0.02), and poor general condition at diagnosis (ECOG 3 and 4) (HR = 10.69; 95% CI[4.42-25.85]; p<0.005). Additionally, a trend towards a higher frequency of de novo resistance was observed in the PD-L1 >50% group (7% vs. 17%, p = 0.19). Conclusion: High PD-L1 expression was more commonly found in lung adenocarcinomas with uncommon and complex EGFR mutations. Furthermore, high PD-L1 expression independently predicted poor survival. These findings warrant validation through prospective studies. Competing Interests: The authors have declared that no competing interests exist. (Copyright: © 2024 Slomka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) |
Databáze: | MEDLINE |
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