Evaluation of the significance od ROS1 expression in NSCLC patients treated with immunotherapy

Introduction: Although immune checkpoint inhibitors (ICIs) have significantly improved survival in patients with lung cancer and high PD-L1 expression (TPS ≥ 50%), the therapeutic response within this group remains heterogeneous. This study aimed to investigate how low and moderate ROS1 protein expression affects the overall survival (OS) of patients receiving immunotherapy as their primary treatment modality. Methods: The study was designed as a retrospective, observational analysis including 18 patients with non-small cell lung cancer (NSCLC), stages III and IV, treated at the University Clinical Centre of the Republic of Srpska. Patients were divided into two groups. The first group was the experimental group (n=9) with patients with immunohistochemically (IHC) confirmed low (1+) or moderate (2+) ROS1 protein expression (clone SP384) and control group (n=9) with patients who were ROS1-negative. A common criterion for both groups was high PD-L1 expression (TPS ≥ 50%). Survival analysis was performed using the Kaplan-Meier method with the Log-Rank test. Results: Survival analysis revealed a statistically significant difference between the groups (χ2 = 5,407; df= 1; p = 0,020). Despite high PD-L1 status, patients with ROS1-positive tumors achieved significantly shorter overall survival compared to the control group. Conclusion: Immunohistochemical detection of the ROS1 protein, even at low staining intensities, represents a significant negative predictive factor for the success of immunotherapy in patients with NSCLC. These findings indicate that patients with any degree of ROS1 expression might derive greater clinical benefit from the early administration of targeted tyrosine kinase inhibitor (TKI) therapy compared to standard immunotherapy.