Advanced non-small-cell lung cancer: how to manage non-oncogene disease

The therapeutic approach to patients affected by advanced non-small-cell lung cancer (NSCLC) is facing rapid and continuous evolution. In recent years, the emergence of new treatment strategies, such as immunotherapy and tyrosine kinase inhibitors, has revolutionized the treatment algorithm and the prognosis of patients with NSCLC. In the non-oncogene-addicted disease, immune-checkpoint inhibitors, either as single agents or combined with chemotherapy, outperformed standard chemotherapy in both untreated and previously treated patients. However, many patients still do not derive the expected benefit from current treatments. Despite representing the only biomarker currently used in clinical practice to guide treatment selection, PD-L1 expression has been proven an imperfect predictor of immunotherapy outcomes. The evaluation of clinical factors remains essential to detect patients that would benefit the most from a particular treatment approach, but the identification of additional biological and molecular predictive tools is a priority. Herein, we provide a comprehensive though concise review of the current treatment approaches to advanced NSCLC in patients without molecular driver alterations, with an additional focus on special populations, concomitant medications, and other considerations that might be useful for daily clinical practice.