Osimertinib (Tagrisso?) is an oral, CNS-active, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets EGFR TKI-sensitizing mutations and, crucially, the T790M mutation that often underlies acquired resistance to EGFR TKI therapy. Osimertinib has been approved in numerous countries for use in patients with T790M-positive advanced NSCLC. In the pivotal, international AURA3 trial in patients with T790M-positive advanced NSCLC who had disease progression after EGFR TKI therapy, osimertinib treatment significantly prolonged progression-free survival (PFS; primary endpoint) compared with platinum-pemetrexed therapy at the time of the primary analysis. PFS results were consistent across predefined subgroups of patients, including those with CNS metastases at baseline. There was no difference between treatment groups in overall survival at 26% maturity. Objective response rates (ORRs) and patient-reported outcomes for prespecified symptoms were also significantly improved with osimertinib relative to platinum-pemetrexed, with CNS ORRs in patients with CNS metastases more than twofold higher in the osimertinib than in the platinum-pemetrexed group. Osimertinib had a manageable tolerability profile, with relatively few patients permanently discontinuing treatment because of adverse events (AEs). With limited treatment options available in this setting, osimertinib is an important option in adult patients with advanced EGFR T790M-positive NSCLC.
