Immunotherapy in oncogene addicted non-small cell lung cancer

The use of immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) has led to notable changes in treatment strategies for patients with advanced non-small cell lung cancer (NSCLC) and now forms a part of standard of care treatment in patients with advanced disease. However, most patients do not respond to ICI monotherapy, which may be explained by significant variations in efficacy according to different immune and molecular profiles in tumours. Improved response rates have been observed in smokers and are associated with tumors that have high mutation loads, with a higher tendency to form neoantigens. This premise itself defies the eventual significance of ICIs for oncogene-driven NSCLC, which in general are more common in never smokers and potentially have reduced capacity for neoantigen formation. Furthermore, pivotal trials investigating ICIs in advanced NSCLC have usually excluded patients with oncogenic drivers, hence the outcome of these agents in this population is poorly characterized. In this article, we aim to review the most current evidence, encompassing clinical and preclinical data focused on a wide range of oncogene-addicted NSCLCs.