Deborah K. Armstrong, MD
Discussant of the SORAYA trial, Deborah K. Armstrong, MD, of Johns Hopkins Kimmel Cancer Center Baltimore, underscored the strong rationale for targeting folate receptor alpha in ovarian cancer.
“There is limited expression [of folate receptor alpha] in normal tissues, limited to the choroid plexus, proximal renal tubules, placenta, and endometrium,” said Dr. Armstrong. “On the other hand, the high-level expression of folate receptor alpha in ovarian cancer correlates with advanced stages of disease and more malignant phenotypes. Alternate cellular folate uptake by the reduced folate carrier circumvents folate deficiency when folate receptor alpha is targeted.”
Folate receptor alpha–targeting approaches include monoclonal antibodies such as farletuzumab and several antibody-drug conjugates, including mirvetuximab soravtansine. There are also folate receptor–based immune approaches with vaccines and chimeric antigen receptor T-cell therapies currently being studied.
“The response rate of 32.4% is importantly maintained in more heavily pretreated patients and in those with prior PARP inhibitor therapy,” said Dr. Armstrong. “Mirvetuximab soravtansine response rates compare quite favorably with those of other treatments in platinum-resistant ovarian cancer.”
Additional Considerations
According to Dr. Armstrong, the only better reported response rates in platinum-resistant ovarian cancer have come from the paclitaxel-plus-bevacizumab subgroup of the AURELIA trial. However, unlike the SORAYA study, these patients had not received prior bevacizumab.1
“Mirvetuximab soravtansine demonstrated clinically meaningful and durable antitumor activity in platinum-resistant, bevacizumab-pretreated ovarian cancer. However, this study did exclude platinum-refractory disease and those with endometrioid, clear cell, and mucinous histologies,” said Dr. Armstrong.
“It’s also unclear what percentage of patients with platinum-resistant ovarian cancer are expected to meet the definition of folate receptor alpha–high used in SORAYA,” she continued. “This outlines the need for a consistent, reproducible, and user-friendly assay or biomarker for folate receptor alpha expression and for an agreed-upon definition of folate receptor alpha–high.”
“The need for anticipatory ocular prophylaxis and ophthalmology care may also be a hurdle in low-resource settings,” Dr. Armstrong added.
DISCLOSURE: Dr. Armstrong has served as a consultant or advisor to AbbVie and Eisai; has received institutional research funding from AstraZeneca, Clovis Oncology, Eisai, Pfizer, and Syndax; and has held other relationships with AstraZeneca.
REFERENCE
1. Pujade-Lauraine E, Hilpert F, Weber B, et al: Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol 32:1302-1308, 2014.
