State of the art: oncogene-driven stage IV non-small-cell lung cancer

Background Two decades ago, stage IV non-small-cell lung cancer (NSCLC) was associated with a poor median overall survival (mOS) of 7-9 months following chemotherapy. Due to revolutionary developments in recent years and the approval of modern targeted therapies, new therapeutic options with remarkable survival times have broadened the therapeutic armamentarium for patients with NSCLC. Objectives This article provides a systematic overview of the latest therapeutic standards in the treatment of stage IV NSCLC, especially concerning targeted therapies, mechanisms of resistance, and future developments. Materials and methods An up-to-date analysis of the literature was performed. Results Molecular testing is essential to offer individualized targeted therapies tailored to corresponding genetic alterations. Besides tyrosine kinase inhibitors (TKI) of EGFR and ALK alterations that have been widely adopted in routine practice for at least a decade, new inhibitors for KRAS G12C, ROS1, BRAF V600, MET exon 14 skipping, NTRK or RET alterations were approved in recent years. Conclusion Due to consistent testing and the use of targeted therapies, prolonged overall survival and improvement in quality of life in patients with NSCLC harboring driver alterations could be achieved. Future developments focus on individualization of targeted therapies, optimization of therapeutic concepts, and identification of new targets.