Novel Antibody-Drug Conjugates in Ovarian Cancer
Posted: Monday, February 25, 2019
Antibody-drug conjugates may be used to bind antigens that are overexpressed on ovarian cancer cells to increase the therapeutic efficacy of cytotoxic agents and decrease their off-target effects. Daphne Stewart, MD, and Mihaela Cristea, MD, of the City of Hope National Medical Center, Duarte, California, published a review of these novel agents in the management of platinum-resistant ovarian cancer in Current Opinion in Obstetrics and Gynecology.
“With appropriate antigen selection and adequate, measurable antigen threshold targets, these new agents may provide an improved strategy for overcoming resistance to standard chemotherapy in ovarian cancer,” proposed the authors.
Although there are no currently approved antibody-drug conjugates in this gynecologic cancer, mirvetuximab soravtansine (IMGN853) has shown single-agent activity and a favorable toxicity profile in folate receptor alpha (FRα)-positive, platinum-resistant, epithelial ovarian cancer. Tumors with moderate to high FRα expression that have not been heavily treated showed the greatest response to mirvetuximab soravtansine.
Furthermore, the phase III FORWARD I trial, in which patients will be randomly assigned to receive either mirvetuximab soravtansine or a single-agent chemotherapy of the physician’s choice, has completed accrual. The phase Ib FORWARD II trial previously demonstrated that mirvetuximab soravtansine may be combined with bevacizumab, carboplatin, and pegylated liposomal doxorubicin.
Other antibody-drug conjugates being evaluated in phase I clinical trials for ovarian cancer target NaPiB2, mesothelin, and the transmembrane glycoprotein MUC16.
Disclosure: The study authors’ disclosure information may be found at lww.com.