Single-center retrospective cohort study of AXL expression to predict resistance to immunotherapy in metastatic non-small cell lung cancer

While PD-1/PD-L1 immunotherapies have improved outcomes of metastatic non-small cell lung cancer (mNSCLC), predictive biomarkers are limited. A retrospective study at the University Hospital of Reims (France) evaluated the association of tumor expression of the receptor tyrosine kinase AXLwith clinical outcomes of mNSCLC patients receiving first-line immunotherapy or chemotherapy from 2015 to 2023. The study included 89 patients without actionable genetic alterations. AXL expression was positive (>1% TPS) in 47 patients. AXL-positive tumors were associated with shorter progression-free survival (4.3 versus 5.3 months; p=0.044). Immunotherapy improved PFS (7.6 versus 4.4 months; p=0.006) and response rate (48% versus 22%) compared with chemotherapy. However, AXL-positive patients derived less benefit from immunotherapy; immunotherapy-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. The authors conclude that AXL expression in associated with reduced immunotherapy efficacy in mNSCLC and may serve as a predictive biomarker (visual abstract).