Biomarker-Targeted Therapies Expand Treatment Selection Beyond Platinum Sensitivity in Recurrent Ovarian Cancer

Clinical Summary: 

• Rebecca Porter, MD, examines the evolving treatment landscape for recurrent ovarian cancer, including the integration of antibody-drug conjugates, biomarker-targeted therapies, and molecular profiling alongside traditional platinum sensitivity-based treatment selection. 
• Antibody-drug conjugates such as mirvetuximab soravtansine and trastuzumab deruxtecan have expanded treatment opportunities, while emerging agents demonstrate activity across varying target expression levels, raising questions about optimal biomarker thresholds and testing strategies.
• These developments highlight the importance of integrating platinum-free interval, tumor biomarkers, prior treatment exposure, and patient characteristics to individualize therapy as novel antibody-drug conjugates and targeted approaches expand treatment options for recurrent ovarian cancer. 

Rebecca Porter, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, discusses the evolving treatment landscape for recurrent ovarian cancer and how antibody-drug conjugates and biomarker-targeted therapies are reshaping treatment selection beyond traditional platinum sensitivity. 

Dr Porter reviews the role of FRα and HER2 testing in identifying patients for targeted therapies, including mirvetuximab soravtansine and trastuzumab deruxtecan, while highlighting emerging antibody-drug conjugates that may demonstrate activity across different levels of target expression. She also discusses the continued importance and limitations of platinum-free interval and how molecular characteristics, prior therapies, and patient preferences can inform individualized treatment decisions.

Transcript: 

Hi, I'm Rebecca Porter. I'm a GYN medical oncologist at the Dana-Farber Cancer Institute, and I'm really happy to be taking part in the debates at the Great Debates Solid Tumors this weekend here in New York City. 

My topic is focusing on patients with recurrent ovarian cancer and how the development of antibody-drug conjugates (ADCs) and other biomarker targeted therapies may change the way we think about treating our patients beyond just platinum sensitivity.

This is a really relevant topic, the treatment landscape for patients with recurrent ovarian cancer, especially those with platinum-resistant, but also with platinum-sensitive disease, has really been expanding recently. I think most notably with the incorporation of ADC options, but also with improvements to weekly taxane-based regimens and other novel treatment strategies that are in clinical trial development. It really brings up this question of should we be thinking about biomarker testing to select therapy for our patients?

We're doing this already with some of the ADCs that are already FDA approved, like mirvetuximab, which does have approval with a companion diagnostic. The approval really is for patients with high folate receptor alpha expression in their tumors. That is really part of standard of care, the testing for that FR-alpha expression. Similarly, testing for HER2 with trastuzumab deruxtecan. 

But some of the newer ADCs that are coming along in development, even the FR-alpha targeting ones with the newer payloads, are showing signs of activity across FR-alpha expression. This really brings up the question of how do we use biomarkers, or if we use biomarkers to select treatments for our patients?

One key consideration is that not all the targets for ADCs have a validated biomarker assay yet. Even if so, we don't quite know yet how expression of the target correlates with clinical activity and how that may change temporally over time.

These are all key questions that will need to be answered to improve how we use biomarkers to select therapies for our patients and to really prioritize target selection. 

The concept of platinum sensitivity still remains really important. The platinum-free interval has been one of the most important prognostic indicators for our patients over the years. It has a lot of value in still considering. It also has limitations though. It doesn't consider histology or molecular features of the tumor, prior lines of therapy patients have had, or patient goals and characteristics. 

When selecting from the expanding treatment options for our patients with recurrent ovarian cancer, we really must integrate both patient characteristics, yes, platinum-free interval is important, but also what we know about biomarker expression and molecular features of the tumor. 

At this point, I think this is still sort of a patient-specific analysis that needs to happen when selecting these therapies.