Introduction: Several targetable genetic alterations have been identified in non-small cell lung cancers (NSCLC) and drugs targeting these alterations have been approved for the management of advanced NSCLC patients. Driver mutations with emerging clinical trial data include EGFR exon 20 insertion mutations, MET amplification, KRAS G12 C point mutations, RET rearrangements, HER2 amplification and mutations, and FGFR amplification and translocations.
Areas covered: We reviewed English-language articles indexed in Medline and PubMed up to the 1st of June 2020. In addition, the proceedings of major conferences were reviewed for relevant abstracts. We report data published regarding targeted therapies which are currently approved and for those which are emerging in advanced or metastatic NSCLC.
Expert review: While these drugs have been shown to be efficacious and tolerable, resistance almost always develops. Though next-generation tyrosine kinase inhibitors (TKIs) have been developed, the appropriate sequencing of these drugs is not clear. Evaluating combination therapies to prevent or delay the onset of resistance and understanding mechanisms of resistance are critical areas of emerging research.
Keywords: Non-small cell lung cancer; mechanisms of TKI resistance; oncogenic driver mutation; targeted therapy; tyrosine kinase inhibitors (TKIs).