Human lung cancer cells injected through mouse-tail vein colonize mouse lungs within 24 h and form lung tumors in about 30 days.
Pretreatment of mice with weekly or daily dosing of erlotinib reduces but does not abolish tail vein injected lung cancer cells to form lung tumors.
Pretreatment of mice with weekly or daily dosing of osimertinib abolish lung cancer cells injected through a tail vein to form lung tumors.
The low-dose once-a-week adjuvant osimertinib could have lower toxicity, higher affordability, and potentially affect acquired resistance.
The recently conducted ADAURA trial concludes daily dosing of adjuvant osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), improves disease-free survival with stage IB/II/IIIA EGFR -mutated non-small cell lung cancer patients in comparison to placebo. We have developed a preclinical orthotopic mouse model, using luciferase tagged lung adenocarcinoma cells harboring EGFR TKI sensitive exon 19 deletion to model and extend trial implications comparing a weekly vs daily dosing outcome of osimertinib to a first-generation TKI- erlotinib. We find that 100% of mice in both the groups receiving osimertinib daily or weekly before injection of cells show a complete absence of homing of cells in mice's lungs from day three until day 18 post-injection of cells. On the other hand, 25% and 75% of mice receiving erlotinib daily and weekly before injecting cells show homing of cells to the lungs. The tumors observed in the lungs, when dissected at day 30, confirmed the colonization of the injected cells homing to the organ. Thus, our study establishes the efficacy of pretreatment with osimertinib in reducing tumor cells' homing to mouse lungs in an in vivo mouse model.