NCOA-RET fusion as a secondary resistance mechanism to osimertinib in complex EGFR-mutated lung adenocarcinoma: Case report and review of literature

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated remarkable efficacy for use in advanced non-small-cell lung cancer (NSCLC). However, the inevitable acquisition of resistance mutations to targeted TKI therapy remains the primary cause of treatment failure. We present a case of a patient with EGFR L858R-positive lung adenocarcinoma who developed resistance to erlotinib through EGFR T790M and later developed secondary resistance with HER2 amplification and a rare NCOA4-RET fusion mutation following treatment with osimertinib. Finally, we demonstrate the application of combination therapy with osimertinib with the RET inhibitor, pralsetinib.