BACKGROUND: Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), significantly improves the prognosis of patients with METHODS: We established osimertinib-resistant cell lines (H1975-OR and PC9-OR) and evaluated the effects of osimertinib, anlotinib, and their combination on cell proliferation RESULTS: Combination osimertinib and anlotinib therapy did not have an obvious synergistic antiproliferative effect in parental H1975 and PC9 cells
however, anlotinib reversed osimertinib resistance in osimertinib-resistant H1975-OR and PC9-OR cells CONCLUSIONS: In conclusion, anlotinib did not significantly enhance the anti-tumor effects of osimertinib in osimertinib-sensitive NSCLC cell lines or a zPDX model. However, it partially reversed osimertinib resistance. This combination therapy may improve the outcomes of patients with advanced NSCLC showing osimertinib-resistance.