Abstract
The advancement of genetic research has changed the treatment management of non-small cell lung cancer (NSCLC) and opened the era of personalized medicine. Currently, three generations of EGFR tyrosine kinase inhibitors (TKIs) are used in the treatment of NSCLC patients with activating mutations in the EGFR gene, and ongoing clinical trials examine the safety and effectiveness of new third and fourth generations. Osimertinib, a third generation of TKIs that binds irreversibly to abnormal tyrosine kinase, may be applied in various indications in patients with NSCLC: (i) in the second and subsequent lines of therapy in patients with resistance to first-generation or second-generation EGFR TKIs, (ii) in the first line of treatment in monotherapy in NSCLC patients with frequent or rare EGFR mutations, (iii) in combination with chemotherapy in patients with locally advanced or metastatic NSCLC with frequent EGFR mutations, (iv) in consolidation therapy in patients with locally advanced NSCLC who had previously received chemoradiotherapy, (v) in adjuvant treatment of NSCLC patients with stage IB-IIIA undergoing radical surgical resection. Despite the high efficacy of osimertinib in NSCLC patients harboring EGFR mutations, resistance driven in EGFR-dependent or EGFR-independent mechanisms may occur. Since resistance to osimertinib is poorly understood, the following review presents the overview of resistance mechanisms to osimertinib, methodological approaches for the resistance diagnosis, and the up-to-date treatment possibilities for overcoming the resistance process.