Osimertinib as First-Line Treatment in EGFR-Mutated Non–Small-Cell Lung Cancer

Genetic analysis is now routine in metastatic non–small-cell lung cancer (NSCLC) to identify somatic sensitizing mutations in EGFR, typically L858R and exon 19 deletion (Ex19del). Patients with these genotypes are treated with first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) (e.g., erlotinib, gefitinib, and afatinib) preferentially over chemotherapy owing to their marked superiority in tumor response, progression-free survival, and quality of life. Such molecular selection has seen median overall survival increase among patients with such genetic variants, from a median of 7.9 months in 20021 to 27.3 months in 2015.2 However, despite rapid and durable responses, acquired . . .