Oncogenic Addictions in Advanced NSCLC: Clinical Insights from Routine Molecular Profiling

Abstract

Non-small cell lung cancer (NSCLC) exhibits significant molecular heterogeneity. Identifying oncogenic alterations is now a cornerstone of advanced disease management, facilitating access to targeted therapies. This study aimed to delineate the molecular landscape of NSCLC and evaluate the prevalence of major oncogenic drivers in our routine clinical practice. We conducted a retrospective analysis of 127 patients diagnosed with stage III or IV NSCLC between June 2023 and June 2025. Demographic, histological, and smoking history data were extracted. Molecular profiling focused primarily on EGFR mutations, alongside ALK and ROS1 rearrangements. The cohort had a mean age of 65.6 years (range: 30–88), with a strong male predominance (89.8%). Most patients (69.3%) reported a smoking history. Adenocarcinoma was the leading histology (70.1%), followed by squamous cell carcinoma (22.0%). Among the 59 patients tested for EGFR, mutations were detected in 16.9% (n=10). ALK and ROS1 rearrangements were identified in 7 and 6 patients, respectively, including 2 cases of ALK/ROS1 co-alteration. These results underscore the actionable mutational burden within this specific population. Systematic molecular profiling is imperative in advanced NSCLC. The detection of specific oncogenic drivers allows for the concrete integration of precision medicine and optimizes the selection of candidates for targeted therapies. Broadening the scope of routine molecular testing remains a critical priority to improve therapeutic outcomes.