Carving out another slice of the pie: Exceptional response to single agent imatinib in an asian female never-smoker with advanced NSCLC with a de-novo PDGFR-α N848 K mutation

Lung Cancer. 2018 Oct:124:86-89. doi: 10.1016/j.lungcan.2018.07.043. Epub 2018 Jul 31.

Abstract

Non-small cell lung cancer (NSCLC) has emerged as a paradigm for clinical application of precision medicine as optimal therapy is commonly chosen based on genomic biomarkers identified in a patient's tumor sample. Recurrent driver alterations are well described, however, a need to continually identify rare variants remains clinically relevant. We identified an incident case of advanced NSCLC with a PDGFR-α N848 K activation loop mutation with no other concurrent oncogenic drivers. Amino acid sequence alignment confirmed homology to the imatinib-sensitive KIT N822 K activation loop mutation observed in GIST. The patient achieved a 2-year response to single agent imatinib that is ongoing. While PDGFR-α N848 K is rare among public sequencing databases our cases strongly suggests functional relevance and highlights the importance of studying rare variants in NSCLC.

Keywords: Driver mutation; Imatinib; NSCLC; PDGFRA; Precision medicine.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antineoplastic Agents / therapeutic use*
  • Asian People
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Cigarette Smoking
  • Female
  • Humans
  • Imatinib Mesylate / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Mutation / genetics*
  • Neoplasm Staging
  • Pneumonectomy
  • Progression-Free Survival
  • Receptor, Platelet-Derived Growth Factor alpha / genetics*
  • Remission Induction

Substances

  • Antineoplastic Agents
  • Imatinib Mesylate
  • Receptor, Platelet-Derived Growth Factor alpha