Tyrosine kinase inhibitors have dramatically changed the clinical outcomes for patients with advanced non-small cell lung cancer with epidermal growth factor receptor mutations. However, there are still challenges in the management of patients with this mutation in a metastatic setting, such as intrinsic and acquired resistance to tyrosine kinase inhibitors. We will discuss the latest advances and new strategies in first-line treatment, osimertinib resistance, and exon 20 mutation treatment.

Non–small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related mortality worldwide. The identification of actionable mutations, particularly in the epidermal growth factor receptor (EGFR) gene, has substantially reshaped the therapeutic landscape of this disease. Tyrosine kinase inhibitors (TKIs) have consistently demonstrated improvements in progression-free survival and overall survival compared with conventional chemotherapy. However, acquired resistance inevitably develops in most patients, driven by secondary mutations, activation of alternative signaling pathways such as MET or HER2, or histologic transformation. In recent years, the management of EGFR-mutatedNSCLC has evolved toward more complex strategies, including first-line combination approaches, treatment intensification with chemotherapy, and the use of bispecific antibodies. In addition, targeted ...