Path Less Traveled: Targeting Rare Driver Oncogenes in Non-Small-Cell Lung Cancer.

Abstract

Over the past decade, tremendous efforts have been made in the development of targeted agents in non-small-cell lung cancer (NSCLC) with nonsquamous histology. Pivotal studies have used next-generation sequencing to select the patient population harboring oncogenic driver alterations that are targetable with targeted therapies. As treatment paradigm rapidly evolves for patients with rare oncogene-driven NSCLC, updated comprehensive overview of diagnostic approach and treatment options is paramount in clinical settings. In this review article, we discuss the epidemiology, molecular testing, and landmark clinical trials addressing the targeted agents for <i>ROS1</i> rearrangement, <i>METex14</i> skipping mutation, <i>EGFR</i> exon 20 insertion, <i>KRAS</i> G12C mutation, <i>HER2</i> mutation, <i>RET</i> fusion, <i>NTRK</i> fusion, and <i>BRAF</i> mutations.