EGFR Mutations in Ovarian Cancer: Rare but Actionable Targets

By: JNCCN 360 Staff
Posted: Tuesday, October 21, 2025

Although epidermal growth factor receptor (EGFR) inhibitors have changed the treatment landscape in non–small cell lung cancer, the real-world prevalence of oncogenic EGFR mutations in ovarian cancer has not been fully assessed. In a multicenter retrospective study reported in JCO Precision Oncology, Gower et al evaluated the prevalence of pathogenic or likely pathogenic EGFR mutations in ovarian cancer, and explored the implications of using EGFR-targeted therapy to treat patients with this rare genomic subset of the disease.  

Study Details 

The investigators consulted the Caris Life Sciences database to review 33,850 ovarian cancer samples that had undergone next-generation sequencing (NGS) of DNA between 2016 and 2025. Pathogenic and likely pathogenic EGFR alterations were identified and classified according to the American College of Medical Genetics and Genomics standards. 

From the initial samples, 27 patients (0.08%) were identified as harboring a somatic genomic alteration that was likely pathogenic or pathogenic. One of these patients, a 72-year-old woman with stage IIIC high-grade serous ovarian carcinoma, carried an EGFR L858R mutation and a TP53 G244D co-mutation. After experiencing disease progression on standard platinum-based chemotherapy and maintenance niraparib, the patient was treated with osimertinib, a third-generation EGFR inhibitor approved for NSCLC with activating EGFR mutations. This targeted therapy induced durable objective response lasting more than 17 months with no significant adverse effects before disease progression was observed on follow-up positron-emission tomography/computed tomography imaging. 

Clinical Implications 

The authors identified parallels between ovarian cancer and NSCLC, where EGFR inhibitors have transformed outcomes for patients with EGFR-mutant disease. However, they caution that EGFR exon 20 insertion mutations are known to confer relative resistance to osimertinib in NSCLC and may have a similar effect in ovarian cancer, where they comprise nearly one-fifth of EGFR mutations. According to the authors, future ovarian cancer trials to evaluate amivantamab, a bispecific EGFR-MET antibody that is currently approved for EGFR exon 20–mutant NSCLC, would be clinically beneficial. 

The real-world data presented in this report constitute the first and largest systematic assessment of the prevalence of oncogenic EGFR mutations in ovarian cancer. It is also the first case reported of a patient with EGFR-mutated ovarian adenocarcinoma treated with osimertinib. The authors demonstrated that despite the rarity of oncogenic EGFR mutations in ovarian cancer, they may represent genuine therapeutic opportunities. 

“This case, in addition to a review of a large genetic database, suggests benefit for EGFR inhibition in EGFR-mutated ovarian cancer, which is a rare, yet actionable target. Treatment in more patients will be required to determine durability of responses and mechanisms of resistance. Meanwhile, this provides evidence that comprehensive NGS may add potential value for treatment strategies in ovarian cancer,” the authors concluded 

Disclosure: For full disclosures of all study authors, visit ascopubs.org. 

JCO Precision Oncology

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