Objective:

To determine the genomic and immunogenic characteristics associated with HER2 expressing epithelial ovarian cancer (EOC) and understand treatment response mechanisms.

Approach:

• Patient Selection: 130 EOC patients were retrospectively identified from an internal clinical genomic database.
• Genomic Analysis: Genomic characteristics were stratified by gastric HER2 score and analyzed using Fisher’s exact test.
• Immunohistochemistry: 34 EOC tumors were stained for HER2 and analyzed for PD-L1, CD4, and CD8 expression.
• Cell Line Treatment: EOC cell lines were treated with T-DXd, assessing PD-L1 and VEGFA levels via quantitative PCR.
• Combination Treatment Analysis: VEGF expression was evaluated following combinatorial treatment with T-DXd and bevacizumab.

Key Findings:

• No significant differences in HRD, CCNE1 amplification, and ARID1A status between HER2 high and low tumors.
• HER2 high tumors showed lower FOLR1 positivity and higher PD-L1 positivity.
• Intratumoral PD-L1 expression and CD4+ T cell levels were significantly higher in HER2 high tumors.
• T-DXd treatment downregulated PD-L1 and VEGFA expression.
• Combination treatment with bevacizumab and T-DXd reduced VEGF expression.

Interpretation:

HER2 high EOC tumors are characterized by specific immunogenic features, and T-DXd may enhance the efficacy of immunotherapy and anti-angiogenic treatments.

Limitations:

• The study is retrospective and based on a limited patient cohort.
• Statistical significance was not achieved for some findings.

Conclusion:

Further examination is warranted to explore the synergy of immunotherapy and anti-angiogenic treatments with T-DXd in EOC.