Treating mutation resistance in non-small cell lung cancer - role of osimertinib.

The discovery of mutations in significantly changed the treatment paradigm of patients with -mutant non-small cell lung cancer (NSCLC), a particular group of patients with different clinical characteristics and outcome to -wild-type patients. In these patients, the treatment of choice as first-line therapy is first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, or afatinib. Inevitably, after the initial response, all patients become refractory to these drugs. The most common mechanism of acquired resistance to EGFR-TKIs is the development of a second mutation in exon 20 of (). Osimertinib is a third-generation EGFR-TKI designed for overcoming -mediated resistance. Based on the results of efficacy and tolerability of Phase II and Phase III studies, osimertinib has been approved for treatment of advanced mutation NSCLC following progression on a prior EGFR-TKI. Occurrence of acquired resistance to osimertinib represents an urgent need for additional strategies including combination with other agents, such as other targeted therapies or checkpoint inhibitors, or development of new and more potent compounds.