Combination of osimertinib and anlotinib enhances anti-proliferative activities in non-small-cell lung cancer

Lung cancer is associated with high mortality, which is predominately comprised of non-small cell lung cancer (NSCLC) cases. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors comprise one of the most common targeted therapies for NSCLC. To understand the anti-proliferative activities of the combination of osimertinib and anlotinib in NSCLC, human NSCLC mutant cells (EGFR T790M NSCLC) were treated with osimertinib and/or anlotinib in our study. The significant decline in cell viability, an increase in cell cycle arrest in the G0/G1 phase, and an increase in apoptosis confirmed the anti-proliferative activities of anlotinib and osimertinib against EGFR T790M NSCLC cells. The anti-proliferative activities of a concomitant combination of anlotinib and osimertinib was better than that of sequential combinations, as well as that with anlotinib or osimertinib treatment alone. Moreover, a decrease in the phosphorylation of EGFR, PI3K, AKT, and ERK indicated that anlotinib and osimertinib inhibited activation of the PI3K/AKT and MAPK/ERK signaling pathways. The inhibitory effect of the concomitant combination of anlotinib and osimertinib on EGFR signaling was more effective than that with sequential combinations, as well as that with anlotinib or osimertinib alone. Our findings suggest that the concomitant combination of anlotinib and osimertinib enhances their anti-proliferative activities against EGFR T790M NSCLC.