This article reviews the development of treatments for non-sleep-related lung cancer (NSCLC) with EGFR mutations, which occur in 10-15% of patients in the US and 50% in Asia.2[3] The most common mutations are deletions in exon 19 and L858R in exon 21, which account for 85-90% of all EGFR mutations and lead to the continued growth of cancer cells.[1]The phase 3 FLAURA2 study demonstrated that the combination of osimertinib with platinum-based chemotherapy and pemetrexed significantly improved overall survival in patients with newly diagnosed advanced EGFR-mutated NSCLC versus osimertinib alone.[2][3][5] This combination achieved a median overall survival of nearly 4 years, the longest recorded in such a phase 3 trial. osimertinib plus chemo was approved by the FDA in February 2024 based on previous results of prolonged progression-free survival.[2] For uncommon mutations such as G719X, L861Q, and S768I, dacomitinib has shown favorable activity with manageable toxicity in a cohort study.Dacomitinib has been associated with resistance abnormalities such as EGFR C797S in 7 cases and other abnormalities as the disease progresses.Treatment involves a choice between monotherapy and combinations based on patient prognosis.[2][3