Antibody-Drug Conjugates in Gynecologic Oncology: Advances, Challenges, and Future Directions

Antibody-drug conjugates (ADCs) have emerged as an efficacious and promising treatment for advanced gynecologic cancers. These agents are an innovative treatment strategy that combines a monoclonal antibody, a linker, and a cytotoxic payload. Currently, three ADCs have received Food and Drug Administration (FDA) approval for use in gynecologic malignancies: mirvetuximab soravtansine, tisotumab vedotin, and trastuzumab deruxtecan. The demonstrable efficacy of these therapeutic agents has catalyzed rapid advancements in the field, prompting investigations into novel antigen targets such as cadherin-6 and B7H4, varying payloads, and innovative construction designs in both preclinical and clinical settings. While enthusiasm for ADCs is substantial, their clinical utility is tempered by significant side effects, such as ocular toxicities and pneumonitis, that necessitate specialized management expertise. Furthermore, the inherent complexities of these drugs and their mechanisms of action underscore the need for further research into the relevance of biomarkers, methods of therapy resistance, and the potential for re-utilization of payloads and targets later in the disease course. This review focuses on the mechanisms of action of ADCs, their developmental trajectory, successes in gynecologic cancers, emerging areas of investigation, the prospective landscape, and current challenges in the field.