Weekly osimertinib dosing prevents EGFR mutant tumor cells destined to home mouse lungs.
Butle A, Joshi A, Noronha V, Prabhash K, Dutt A.
The recently conducted ADAURA trial concludes daily dosing of adjuvant osimertinib improves disease-free survival in patients with early stage EGFR-mutated non-small cell lung cancer compared to placebo. However, the extent of the benefit of osimertinib over gefitinib or weekly dosing of osimertinib could not be addressed in the study. Here, we present a preclinical orthotopic NOD-SCID mouse model developed using luciferase tagged lung adenocarcinoma cells to model and extend trial implications of the recently conducted ADAURA trial.
We compare dosing treatment regimen of the two EGFR-TKIs on homing of luciferase tagged lung cancer cells in mice injected intravenously through the tail vein. Thirty mice were divided into the control, daily and weekly pre-treatment groups involving the respective dosing regimen with the EGFR-TKI’s erlotinib (25 mg/kg) and osimertinib (15 mg/kg). The animals were monitored using bioluminescence imaging for determining the homing of cells to the lungs. We find efficient clearance of PC-9 cells from the lungs of mice with daily and weekly osimertinib pre-treatment group compared to a partial effect in response to the erlotinib pre-treated group.
In summary, our study reveals that low-dose once-a-week osimeritinib EGFR-TKI pre-treatment as a possible treatment option in delaying the onset of disease in patients as an adjuvant treatment post resection of early stage tumors or among patients with pre-disposition to EGFR mutant lung cancers harboring germline EGFR kinase domain mutations. The low-dose once-a-week osimertinib could potentially have several advantages over daily dosing, including lower toxicity, affordability, ease of administration and delaying or preventing acquired resistance that remains to be explored.