Folate receptor alpha as a successful biomarker in the treatment of low-grade serous ovarian cancer patients using preclinical and clinical models
Low-grade serous ovarian cancer is a rare epithelial ovarian cancer subtype characterized by high resistance to chemotherapy. Development of novel, effective, targeted treatments for recurrent low-grade serous ovarian cancer remains an unmet medical need. We evaluated FOLR1 expression in a cohort of low-grade serous ovarian cancer patients and the preclinical and clinical activity of mirvetuximab soravtansine, an antibody-drug conjugate targeting FOLR1, in vivo in a patient-derived xenograft model and in a heavily pretreated low-grade serous ovarian cancer patient progressing after chemotherapy, aromatase inhibitor, and MEK inhibitor treatment. FOLR1 expression was evaluated in 27 low-grade serous ovarian cancer patients using immunohistochemistry. The efficacy of mirvetuximab soravtansine was assessed in vivo in a low-grade serous ovarian cancer patient-derived xenograft model in severe combined immunodeficient mice, as well as in a patient harboring a recurrent low-grade serous ovarian cancer resistant to standard treatment modalities. FOLR1 expression was detected in all 27 (100%) low-grade serous ovarian cancer cases, with 21 of 27 (78%) of the samples demonstrating 2+/3+ in ≥75% of tumor cells. In vivo studies in mice demonstrated that mirvetuximab soravtansine inhibited tumor growth and prolonged survival in a low-grade serous ovarian cancer patient-derived xenograft model derived from a patient progressing after chemotherapy/aromatase inhibitor/MEK inhibitor. Clinical evidence further supported the therapeutic activity of mirvetuximab soravtansine in a FOLR1-positive low-grade serous ovarian cancer patient, as indicated by a prolonged partial response after 8 months of treatment. FOLR1 is overexpressed in a large percentage of low-grade serous ovarian cancers. Mirvetuximab soravtansine may represent a novel treatment option for low-grade serous ovarian cancer patients progressing after standard treatment modalities. Clinical trials with mirvetuximab soravtansine in FOLR1-positive low-grade serous ovarian cancers are warranted.