Rare driver alterations in nonsmall cell lung cancer: novel targeted drugs

Curr Opin Oncol. 2022 Jan 1;34(1):77-82. doi: 10.1097/CCO.0000000000000806.


Purpose of review: The current review presents clinically relevant driver alterations in nonsmall cell lung cancer (NSCLC) and the targeted treatments currently available for clinical use as well as those in clinical trials and advanced stages of drug development.

Recent findings: Mesenchymal-epithelial transition factor, human epidermal growth factor receptor 2, proto-oncogene B-RAF (BRAF), proto-oncogene tyrosine-protein kinase ROS (ROS1), rearranged during transfection (RET) and neurotrophic tyrosine kinase are rare genetic driver alterations, each present in a small subset of patients with NSCLC. Treatments targeting BRAF, ROS1, RET and neurotrophic tyrosine kinase are approved in Europe, and promising treatments targeting mesenchymal-epithelial transition factor and human epidermal growth factor receptor 2 are available in clinical trials and compassionate use programs. The response rates, duration of response and tolerability observed in trials of targeted drugs in this setting are presented in detail here.

Summary: While rare driver alterations are, by definition, rare, their recognition can change the course of NSCLC for those patients affected. Targeted treatments for many rare driver alterations are well tolerated and effective. Screening for molecular changes in advanced NSCLC should include screening for rare drivers, and patients should be directed to clinical trials in setting where treatment of the driver alterations is not otherwise available.

Publication types

  • Review

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / therapeutic use
  • Proto-Oncogene Proteins B-raf / genetics


  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins B-raf