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AXL expression to predict resistance to immunotherapy in metastatic non-small cell lung cancer
Julien Ancel1, Maxime Dewolf2, Béatrice Nawrocki-Raby3
1Université de Reims Champagne-Ardenne, INSERM, P3Cell, UMR-S 1250, Reims, France; CHU Reims, Hôpital Maison Blanche, Service de Pneumologie, Reims, France.
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.
Insights
AXL expression in non-small cell lung cancer (NSCLC) predicts poor response to immunotherapy. Targeting AXL may improve treatment outcomes for NSCLC patients receiving immunotherapy.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Discovery
Background:
- Non-small cell lung cancer (NSCLC) presents significant therapeutic challenges.
- Predictive biomarkers for PD-1/PD-L1 immunotherapies in NSCLC are limited.
- AXL receptor tyrosine kinase is linked to poor prognosis and may affect treatment response.
Purpose of the Study:
- To evaluate the association between AXL expression and clinical outcomes in advanced NSCLC patients.
- To determine if AXL expression influences response to immunotherapy versus chemotherapy.
Main Methods:
- Retrospective analysis of 89 metastatic NSCLC patients treated with anti-PD-1 therapy or chemotherapy.
- Assessment of AXL expression via immunohistochemistry.
- Analysis of progression-free survival (PFS) and overall survival (OS), adjusted for prognostic variables using propensity score matching.
Main Results:
- AXL-positive NSCLC tumors correlated with shorter PFS.
- Immunotherapy improved PFS and response rates compared to chemotherapy.
- AXL-positive patients showed diminished benefit from immunotherapy; AXL-negative patients had superior PFS and OS with immunotherapy.
- AXL was an independent predictor of poorer PFS and OS.
- KRAS and STK11 mutations were more prevalent in AXL-positive tumors.
Conclusions:
- AXL expression is linked to reduced immunotherapy efficacy in NSCLC.
- AXL may function as a predictive biomarker for immunotherapy response.
- AXL presents a potential therapeutic target for improving NSCLC treatment outcomes.
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