Identification of targetable <i>EGFR</i> mutations in ovarian cancer.

e17550 Background: Carboplatin and paclitaxel doublet remains the chemotherapy backbone for newly diagnosed ovarian cancer after surgical cytoreduction, along with germline testing for BRCA1 and BRCA2 and testing for homologous-recombination deficiency as standard-of-care. However, comprehensive next-generation sequencing (NGS) of DNA or RNA is not standard for these patients due to the lack of established targeted therapies in ovarian cancer. Here, we evaluated the tumors of ovarian cancer patients with comprehensive molecular profiling to assess for pathogenic or likely pathogenic (P/LP) mutations in the EGFR oncogene. Methods: Retrospective review of 33,850 molecularly profiled ovarian cancer samples from real-world patients that underwent NGS of DNA (592-gene or whole exome) at Caris Life Sciences (Phoenix, AZ) between 2016 and 2024. EGFR-mutated cases were defined as those harboring known P/LP based on the EGFR genomic alteration found by Caris. Results: We detected 27 patients out of 33,850 ovarian cancer cases (0.08%) with a genomic alteration in the EGFR gene that was P/LP (Table 1). Of these 27 cases, 12 patients had EGFR exon 20 mutation (44%), including 5 patients with an EGFR T790M mutation (19%) and 5 patients with an Exon20-insertion mutation (19%). 4 patients had EGFR L858R or Exon 19 deletion mutation (15%) and 3 had an EGFR Exon 18 mutation (11%). Conclusions: Ovarian cancer driven by oncogenic EGFR mutation is a rare occurrence, yet it represents an actionable molecular target with EGFR-directed inhibitors. This highlights the value of comprehensive NGS of DNA in the management of ovarian cancer, ensuring that molecularly targeted therapies are considered for appropriate patients. EGFR genomic alterations found through comprehensive NGS of DNA at caris life sciences in patients with ovarian cancer. EGFR Exon Genomic Alteration Patient(s) % Exon 15 P596S 1 4 Exon 18 G724S; E709 3 11 Exon 19 Deletion 2 7 Exon 20 T790M 5 19 Exon 20 Insertion 5 19 Exon 20 Others 2 7 Exon 21 V834A 1 4 Exon 21 L858R 3 11 Exon 3, 4, 7, 17 A289D 5 19