Birrer Shares Perspective on Folate Receptor Alpha-Targeting Agents in Ovarian Cancer

Published: Wednesday, Apr 17, 2019
Michael Birrer,
Michael Birrer, MD, PhD
Folate receptor alpha (FRα) is an active area of investigation in the ovarian cancer paradigm, as it is highly overexpressed in approximately 60% of patients with high-grade, serous ovarian cancer, explained Michael Birrer, MD, PhD.

What are some common knowledge gaps in ovarian cancer when it comes to these newer approaches in research?
I think we still have a problem with the upfront treatment. We probably cure about 15%, but that number hasn’t changed in 35 years. This is why [the] SOLO-I [trial] is so exciting, in that the PFS curve is pretty flat at the end and had not even reached median PFS, so that is the kind of improvement we need to see more of, and, of course, ultimately stratifying patients according to who will really benefit from the treatment versus toxicity is really important. The other area [in which there] is still an unmet need is the effective treatment of platinum-resistant disease, which is on the other end of the spectrum. Once patients recur, they are incurable, and most tumors will eventually become platinum-resistant. [Patients with] platinum-resistant tumors have a median overall survival of about 11 months and a median PFS of about 6 months.

Given the rapid trajectory of research, how would you assess current efforts emphasizing folate receptor α (FRα) as a target for treatment? 
There is no doubt that FRα is a validated target. It is highly overexpressed in about 60% of high-grade, serous ovarian cancers, probably 25% of endometrial, and some non–small cell lung cancer, also. But it has certainly been validated as a cell-surface target for ovarian cancer. Now, the use of it as a therapeutic target had some starts and stops in terms of using a folate mimetic, which didn’t work out too well. But with mirvetuximab soravtansine, a humanized antibody, the initial data, phase I, and expansion cohorts showed the target to be important and the agent to be quite effective.
How are FRα-targeting agents different from other agents currently used to treat ovarian cancer?
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Community Practice Connections™: 22nd Annual International Congress on Hematologic Malignancies®: Focus on Leukemias, Lymphomas and MyelomaMay 30, 20192.0
Online Medical Crossfire®: 5th Annual Miami Lung Cancer ConferenceMay 30, 20196.5
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