Emerging EML4-ALK Variant 5 as a Concurrent Resistance Mechanism to Osimertinib in a Patient With EGFR E19del/T790M NSCLC

The presence of gain-of-function somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene represents the first molecular subset of patients with metastatic non–small-cell lung cancer (NSCLC) whose tumors respond to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs): objective response rate of 60% to 70% and median progression-free survival (PFS) of 9 to 15 months are seen when used as first-line therapy.1 However, acquired resistance to first- and second-generation EGFR TKIs usually develop within 2 years, with the emergence of secondary T790M mutation as the most common mechanism.