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

Yuki Katsuya; Kentaro Miyake; Takashi Higuchi; Hiromichi Oshiro; Norihiko Sugisawa; Shree Ram Singh; Yasushi Goto; Ming Zhao; Robert M Hoffman

doi:10.21873/invivo.11871

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.

Authors

Yuki Katsuya^{1

2}, Kentaro Miyake^{1

2}, Takashi Higuchi^{1

2}, Hiromichi Oshiro^{1

2}, Norihiko Sugisawa^{1

2}, Shree Ram Singh³, Yasushi Goto⁴, Ming Zhao¹, Robert M Hoffman^{5

2}

Affiliations

¹ AntiCancer, Inc., San Diego, CA, U.S.A.
² Department of Surgery, University of California, San Diego, CA, U.S.A.
³ Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, U.S.A. [email protected] [email protected].
⁴ Department of Thoracic Oncology, National Cancer Center, Tokyo, Japan.
⁵ AntiCancer, Inc., San Diego, CA, U.S.A. [email protected] [email protected].

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