This study examined the real-world effectiveness of osimertinib, a third-generation tyrosine kinase inhibitor, on EGFR-mutated non-small-cell lung cancer. Osimertinib has shown promising results in clinical trials, but this research study looked at how it performs in real-world settings, where patients may have different characteristics than those typically included in trials. This study reviewed data from over 600 patients treated with osimertinib, either as their first (L1) or second metastatic line (L2) of treatment. The results showed that patients who took osimertinib as L1 experienced a median progression-free survival of 12.4 months, compared to 7.4 months for those treated in L2. The presence of brain metastases was associated with a poorer prognosis. Overall survival rates were lower than those reported in clinical trials, likely due to differences in patient conditions, such as older age and worse overall health. This study highlights the challenges of applying trial results to everyday medical practice and emphasizes the need for tailored treatment approaches for patients with advanced lung cancer.