Identification of Targetable <i>EGFR</i> Mutations in Ovarian Cancer.

Abstract

<i>EGFR</i> mutations are classically seen in non-small cell lung cancers (NSCLCs), and EGFR-directed inhibitors have changed the therapeutic landscape in patients with <i>EGFR</i>-mutated NSCLC. The real-world prevalence of <i>EGFR</i>-mutated ovarian cancers has not been previously described. We aim to determine the prevalence of pathogenic or likely pathogenic <i>EGFR</i> mutations in ovarian cancer and describe a case of <i>EGFR</i>-mutated metastatic ovarian cancer with a durable response to osimertinib, an EGFR-directed targeted therapy. Retrospective review of 33,850 molecularly profiled ovarian cancer samples from real-world patients who underwent next-generation sequencing (NGS) of DNA between 2016 and 2025. <i>EGFR</i>-mutated cases were defined as those harboring known pathogenic or likely pathogenic mutations based on the <i>EGFR</i> genomic alteration discovered by Caris. Of 33,850 patients, 27 (0.08%) harbored a genomic alteration in the <i>EGFR</i> gene that was pathogenic or likely pathogenic, including <i>EGFR</i> exon 20 mutation (n = 12, including five patients with <i>EGFR</i> T790M mutation), <i>EGFR</i> L858R (n = 3), and an <i>EGFR</i> exon 19 deletion (n = 2). Only one patient was treated with osimertinib, a third-generation EGFR-inhibitor, and achieved a durable objective response for over 17 months. Ovarian cancer driven by an oncogenic <i>EGFR</i> mutation is a rare occurrence, yet it is an actionable molecular target with EGFR-directed inhibitors. This underlies the potential value of comprehensive NGS in the management of ovarian cancer for discovering actionable genomic alterations.