Dr Monk on Pivotal Biomarkers in Recurrent Ovarian Cancer

“In recurrent ovarian cancer, there are basically three biomarkers that are pivotal.”

Bradley Monk, MD, FACOG, FACS, medical director of the Late-Stage Clinical Research Program at Florida Cancer Specialists & Research Institute, discussed the relevance of folate receptor alpha (FRα), HER2, and PD-L1 expression in influencing therapeutic decision-making in recurrent ovarian cancer.

Monk referred to FRα as a pivotal biomarker in this setting because the antibody-drug conjugate mirvetuximab soravtansine-gynx (Elahere) has been FDA approved since 2024 and represents an important option for patients with FRα-positive disease. However, patient selection is critical, Monk explained. Eligibility depends on immunohistochemistry (IHC) testing, with a requirement that at least 75% of tumor cells demonstrate staining intensity of 2+ or greater. Clinically, FRα overexpression is observed in approximately 35% to 40% of patients with recurrent ovarian cancer, making it a relatively common and actionable biomarker when present.

Monk then shifted focus to HER2, another target that has garnered attention across tumor types. Fam-trastuzumab deruxtecan-nxki (Enhertu) has received accelerated approval from the FDA in a tumor-agnostic context, but its role in ovarian cancer is more limited due to lower prevalence, Monk stated. For treatment consideration, HER2 expression must reach an IHC score of 3+. In contrast to FRα, HER2 overexpression at this level is seen in fewer than 5% of ovarian cancer cases, highlighting its more niche applicability in this disease.

Finally, Monk addressed PD-L1 expression, a key biomarker for immunotherapy. Testing for PD-L1 is performed using combined positive score (CPS), with a threshold of greater than 1 indicating potential eligibility for treatment with pembrolizumab (Keytruda). Notably, PD-L1 positivity at this level is relatively common, occurring in approximately 75% of patients, making it a broadly relevant biomarker in recurrent disease.

Overall, Monk underscored the importance of comprehensive biomarker assessment using immunohistochemistry for FRα, HER2, and PD-L1. These tests not only guide treatment selection but also help identify patients most likely to benefit from targeted therapies and immunotherapy. As the therapeutic landscape continues to expand, integrating biomarker testing into routine clinical practice remains essential for optimizing outcomes in recurrent ovarian cancer.

Check out the OncLive Biomarker Consortium site for more biomarker insights in ovarian cancer and beyond!