Antibody drug conjugates in gynaecological cancers: navigating between opportunities and challenges

Antibody–drug conjugates (ADCs), which are tumor-targeting antibodies conjugated with cytotoxic chemotherapy agents, have emerged as a promising therapeutic approach in gynaecological cancers. Gynaecologicaal tumor-associated antigens targeted by ADCs include folate receptor-α (FRα), HER2, TROP2, tissue factor (TF), CDH6, CLDN6, B7–H4, B7–H3 and NaPi2b. Currently, three ADCs are clinically available for the treatment of gynaecological cancers: Mirvetuximab soravtansine for FRα-positive ovarian cancer, Tisotumab vedotin (targeting TF) for cervical cancer, and Trastuzumab deruxtecan for HER2-positive solid tumors. Various stages of investigation of ADCs as single agent or in combination treatments are ongoing with promising early signs of efficacy. Upon positive results from phase III trials, new treatment options will be available to reshape the standard of care of gynaecological malignancies and improve patients' outcome. This review summarizes the major clinical studies of ADCs in ovarian, endometrial and cervical cancer, and explores the main challenges related to their use in clinical practice.