EML4-ALK Rearrangement as a Mechanism of Resistance to Osimertinib in Metastatic Lung Adenocarcinoma: A Case Report

Abstract Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is the preferred front-line therapy for EGFR-mutant advanced non-small cell lung cancer. However, despite its high initial response rates, multiple EGFR-independent mechanisms of resistance have been reported in patients receiving osimertinib. One such mechanism is the emergence of acquired, targetable oncogenic fusion events. It has been documented in other Case reports that combination therapies can be efficacious in these scenarios. In our case report, we present a patient with EGFR-mutant advanced non-small cell lung cancer who developed an acquired echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement mediating resistance to osimertinib, which was overcome by using a combination of osimertinib with the ALK TKI alectinib.