Identification of Targetable EGFR Mutations in Ovarian Cancer

PURPOSE EGFR mutations are classically seen in non–small cell lung cancers (NSCLCs), and EGFR-directed inhibitors have changed the therapeutic landscape in patients with EGFR -mutated NSCLC. The real-world prevalence of EGFR -mutated ovarian cancers has not been previously described. We aim to determine the prevalence of pathogenic or likely pathogenic EGFR mutations in ovarian cancer and describe a case of EGFR -mutated metastatic ovarian cancer with a durable response to osimertinib, an EGFR-directed targeted therapy. METHODS 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. EGFR -mutated cases were defined as those harboring known pathogenic or likely pathogenic mutations based on the EGFR genomic alteration discovered by Caris. RESULTS Of 33,850 patients, 27 (0.08%) harbored a genomic alteration in the EGFR gene that was pathogenic or likely pathogenic, including EGFR exon 20 mutation (n = 12, including five patients with EGFR T790M mutation), EGFR L858R (n = 3), and an EGFR 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. CONCLUSION Ovarian cancer driven by an oncogenic EGFR 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.