Comparison of the Efficacy of EGFR Tyrosine Kinase Inhibitors Erlotinib and Low-dose Osimertinib on a PC-9-GFP EGFR Mutant Non-small-cell Lung Cancer Growing in the Brain of Nude Mice

In Vivo. 2020 May-Jun;34(3):1027-1030. doi: 10.21873/invivo.11871.

Abstract

Background/aim: Brain metastases are found in approximately 30% of patients with epidermal-growth-factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). We compared the efficacy of two EGFR-tyrosine kinase inhibitors (TKIs), erlotinib and osimertinib on a PC-9-GFP EGFR mutant NSCLC growing in the brain of nude mice.

Materials and methods: The brain metastasis models were randomized into five groups and treated for 15 days: Control; 5 mg/kg erlotinib; 50 mg/kg erlotinib; 0.5 mg/kg osimertinib; 5 mg/kg osimertinib. Tumor volume was evaluated by non-invasive fluorescence imaging.

Results: Only 5 mg/kg osimertinib, a low-dose compared to the clinically-equivalent dose, showed significant tumor regression compared to the control.

Conclusion: This study strongly supports the high activity of osimertinib for intracranial lesions of EGFR-mutant NSCLC.

Keywords: Erlotinib; PC-9-GFP; non-small cell lung cancer; nude mice; osimertinib.

MeSH terms

  • Acrylamides / administration & dosage
  • Acrylamides / pharmacology*
  • Aniline Compounds / administration & dosage
  • Aniline Compounds / pharmacology*
  • Animals
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / secondary*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Drug Synergism
  • Drug Therapy, Combination
  • ErbB Receptors / genetics
  • Erlotinib Hydrochloride / administration & dosage
  • Erlotinib Hydrochloride / pharmacology*
  • Female
  • Genes, Reporter
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Nude
  • Mutation
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology*
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

  • Acrylamides
  • Aniline Compounds
  • Protein Kinase Inhibitors
  • osimertinib
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors