Adenocarcinoma Harboring EGFR-RAD51 Fusion Treated with Osimertinib: A Case Report

Epidermal growth factor receptor (EGFR) mutations are among the most common driver mutations in lung adenocarcinoma. Rare alterations, such as the EGFR-RAD51 fusion, respond to treatment with EGFR tyrosine kinase inhibitors but can be missed by limited genomic sequencing panels. We report a case of metastatic lung adenocarcinoma in a patient who is a never-smoker who initially did not have a targetable alteration identified on two different sequencing panels. Initial response to combination chemoimmunotherapy was short-lived. A rare EGFR-RAD51 fusion was then identified using a more in-depth sequencing panel. The patient experienced a dramatic and durable response to osimertinib. This case highlights the rarity of EGFR-RAD51 fusions, efficacy of EGFR TKIs, and importance of a thorough search for targetable alterations in never-smokers with lung adenocarcinoma.