Transformation to small-cell carcinoma as an acquired resistance mechanism to AZD9291: A case report

Oncotarget. 2017 Mar 14;8(11):18609-18614. doi: 10.18632/oncotarget.14506.

Abstract

AZD9291, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), benefits patients with T790M mutant non-small-cell lung cancer who fail treatment with first-generation EGFR TKIs. Acquisition of resistance to AZD9291 occurs inevitable and mechanisms need to be explored. We reported an advanced lung adenocarcinoma female with EGFR exon19 deletion treated on AZD9291 after failure of erlotinib and chemotherapy. Disease progressed again after 6 months' treatment of AZD9291 with hepatic metastasis. Re-biopsy of the hepatic lesion showed histopathology transformation to small cell lung cancer, which harbored EGFR exon19 deletion. Therefore, small cell carcinoma transformation is one of potential resistance mechanisms to AZD9291 and regimen for small cell carcinoma may be one of the treatment options.

Keywords: AZD9291; EGFR-TKI; NSCLC; acquired resistance; transformation.

Publication types

  • Case Reports

MeSH terms

  • Acrylamides / pharmacology*
  • Aniline Compounds / pharmacology*
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Middle Aged
  • Protein Kinase Inhibitors / pharmacology*
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / genetics
  • Small Cell Lung Carcinoma / pathology

Substances

  • Acrylamides
  • Aniline Compounds
  • Protein Kinase Inhibitors
  • osimertinib