Identification of Targetable Mutations in Ovarian Cancer.

Purpose: mutations are classically seen in non-small cell lung cancers (NSCLCs), and EGFR-directed inhibitors have changed the therapeutic landscape in patients with -mutated NSCLC. The real-world prevalence of -mutated ovarian cancers has not been previously described. We aim to determine the prevalence of pathogenic or likely pathogenic mutations in ovarian cancer and describe a case of -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. -mutated cases were defined as those harboring known pathogenic or likely pathogenic mutations based on the genomic alteration discovered by Caris.

Results: Of 33,850 patients, 27 (0.08%) harbored a genomic alteration in the gene that was pathogenic or likely pathogenic, including exon 20 mutation (n = 12, including five patients with T790M mutation), L858R (n = 3), and an 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 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.