Early Assessment of Circulating Tumor Cells and Their PD-L1 Expression as Predictive Biomarkers in Metastatic Non-Small Cell Lung Cancer Patients Treated with Immunotherapy: An Exploratory Study

Abstract

Introduction The prognosis of metastatic non-small cell lung cancer (mNSCLC) has improved in recent years but therapeutic benefit remains heterogeneous, underscoring the need for reliable biomarkers. Liquid biopsy techniques, including the analysis of circulating tumor cells (CTCs) and Programmed death-ligand 1 (PD-L1) expression on CTCs (PD-L1-CTCs), have emerged as promising tools. Materials and Methods We conducted a retrospective study in a cohort of mNSCLC patients treated with Immune Checkpoint Inhibitors (ICIs) to evaluate the predictive value of these biomarkers at baseline and at an early time point during treatment. CTCs were captured with the ClearCell® FX platform and then assessed for PD-L1 by immunostaining. Therapeutic drug monitoring of nivolumab and pembrolizumab was performed. Results Thirty-seven mNSCLC patients were enrolled. The median CTCs count was 35 CTCs per 7.5 mL of whole blood (standard deviation ± 939). PD-L1-CTCs were detected in 51% of patients. No correlation was found between PD-L1-CTCs and PD-L1 on tumor Formalin-Fixed, Paraffin-Embedded (FFPE) tissue. Higher-than-median CTCs count was associated with a trend toward worse outcomes. In contrast, PD-L1 expression on CTCs did not predict treatment response. Most patients presented a trough concentration of ICI at cure 3 above 10 µg/mL, regardless clinical response. Conclusion Baseline CTCs levels tended to be associated with clinical outcomes, whereas PD-L1 expression on CTCs was not. Early evaluation of changes in these two parameters did not improve outcome prediction under ICI treatment. Larger studies with longer follow-up and more in-depth analyses are warranted to further define the prognostic and predictive value of CTC-based biomarkers.