Targeted therapies and more recently immune checkpoint inhibitors (ICI) have transformed the treatment landscape of advanced NSCLC. Clinical trials investigating immune checkpoint inhibitors (ICI) have usually excluded patients with oncogenic drivers, so that the outcome of these agents in this population is poorly known. In patients with oncogenic addiction, targeted therapy remains clearly the best option, and the place of immunotherapy in this population has not been clearly defined yet.Based on available data, we suggest that (i) immunotherapy single agent should be proposed only after exhaustion of more validated treatments, (ii) combinations of immunotherapy with targeted therapies are of interest provided that we can manage toxicity and find the best sequence, (iii) a combination of immunotherapy with chemotherapy may be appealing in patients pretreated with targeted agents. The best way to opt in for the best strategy will depend upon the identification of adequate biomarkers. New basic and clinical research is awaited in this field.
Keywords: ALK; EGFR; Immunotherapy; Non-small cell lung cancer; Oncogenic addiction; Targeted therapy.