[en] [en] BACKGROUND: Non-small cell lung cancer (NSCLC) remains a major therapeutic challenge. While PD-1/PD-L1 immunotherapies have improved outcomes, predictive biomarkers are limited. AXL, a receptor tyrosine kinase associated with poor prognosis, may impact treatment response. This study evaluates AXL expression and clinical outcomes in advanced NSCLC patients treated with immunotherapy or chemotherapy.
METHODS: This retrospective study included 89 metastatic NSCLC patients treated at the University Hospital of Reims (2015-2023) with either anti-PD-1 therapy or chemotherapy. Clinical data and outcomes-progression-free survival (PFS) and overall survival (OS)-were analyzed. AXL expression was assessed by immunohistochemistry, and propensity score matching adjusted for prognostic variables.
RESULTS: AXL-positive tumors were associated with shorter PFS (4.3 vs. 5.3 months, p = 0.044). Immunotherapy improved PFS (7.6 vs. 4.4 months, p = 0.006) and response rate (48 % vs. 22 %) compared to chemotherapy. However, AXL-positive patients derived less benefit from immunotherapy; IO-treated AXL-negative patients had significantly better PFS (p = 0.003) and OS (p = 0.018). Multivariate analysis identified AXL as an independent factor for poorer PFS (HR 4.15, p = 0.013) and OS (HR 5.634, p = 0.004). KRAS and STK11 mutations were more frequent in AXL-positive tumors.
CONCLUSIONS: AXL expression is associated with reduced immunotherapy efficacy in NSCLC and may serve as a predictive biomarker and therapeutic target.
Disciplines :
Oncology
Author, co-author :
Ancel, Julien ; Université de Reims Champagne-Ardenne, INSERM, P3Cell, UMR-S 1250, Reims, France, CHU Reims, Hôpital Maison Blanche, Service de Pneumologie, Reims, France. Electronic address: jancel@chu-reims.fr
Dewolf, Maxime; CHU Reims, Hôpital Maison Blanche, Service de Pneumologie, Reims, France
Nawrocki-Raby, Béatrice ; Université de Reims Champagne-Ardenne, INSERM, P3Cell, UMR-S 1250, Reims, France
Durlach, Anne; Université de Reims Champagne-Ardenne, INSERM, P3Cell, UMR-S 1250, Reims, France, CHU Reims, Pôle de Biologie Territoriale, Service de Pathologie, Reims, France
Dalstein, Véronique ; Université de Reims Champagne-Ardenne, INSERM, P3Cell, UMR-S 1250, Reims, France, CHU Reims, Pôle de Biologie Territoriale, Service de Pathologie, Reims, France
Lalun, Nathalie; Université de Reims Champagne-Ardenne, INSERM, P3Cell, UMR-S 1250, Reims, France
Dormoy, Valérian ; Université de Reims Champagne-Ardenne, INSERM, P3Cell, UMR-S 1250, Reims, France, Institut universitaire de France (IUF), Paris, France
Deslée, Gaëtan; Université de Reims Champagne-Ardenne, INSERM, P3Cell, UMR-S 1250, Reims, France, CHU Reims, Hôpital Maison Blanche, Service de Pneumologie, Reims, France
Gilles, Christine ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Polette, Myriam; Université de Reims Champagne-Ardenne, INSERM, P3Cell, UMR-S 1250, Reims, France, CHU Reims, Pôle de Biologie Territoriale, Service de Pathologie, Reims, France
Language :
English
Title :
AXL expression to predict resistance to immunotherapy in metastatic non-small cell lung cancer.
URCA - Université de Reims Champagne-Ardenne Amgen GmbH INSERM - Institut National de la Santé et de la Recherche Médicale
Funding text :
With financial support from ITMO Cancer of Aviesan within the framework of the 2021\u20132030 Cancer Control Strategy, on funds administered by Inserm, URCA and with financial support from the Amgen France Fund for Science and Humanity.
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