Clinical significance and safety profile of antibody-drug conjugates in malignancies of the female reproductive system

Abstract

Introduction. Antibody-drug conjugates (ADCs) are expanding the therapeutic landscape of systemic treatment for malignancies of the female reproductive system, particularly in the setting of disease progression following standard chemotherapy. Their efficacy is determined by tumor target expression, antibody structure, cytotoxic payload, and drug-to-antibody ratio. However, increased selectivity of delivery does not reduce the risk of systemic and organ-specific toxicity, including adverse events affecting various organs. Aim: to synthesize data on the clinical significance and safety profile of ADCs currently used or under investigation in ovarian, endometrial, and cervical cancer, with an analysis of the frequency, clinical manifestations, mechanisms, prevention, and management of adverse events. Materials and Methods. An analytical review of publications on ADCs in gynecologic oncology was conducted, including phase I–III randomized trials, reviews, clinical guidelines, and supportive care documents. Agents targeting folate receptor alpha (FRα), tissue factor (TF), human epidermal growth factor receptor 2 (HER2), trophoblast cell surface antigen 2 (Trop-2), and cadherin-6 were analyzed. The analysis included data on molecular characteristics of the agents, antitumor activity, adverse event frequency, grade ≥ 3 toxicity, organ-specific complications, and safety monitoring approaches. Results. The most clinically significant ADCs in gynecologic oncology are mirvetuximab soravtansine, tisotumab vedotin, and trastuzumab deruxtecan; promising data have also been identified for Trop-2- and cadherin-6-targeting conjugates. Mirvetuximab soravtansine is characterized by a predominance of ocular complications, largely unrelated to FRα expression in the cornea. Tisotumab vedotin is associated with ocular toxicity, hemorrhagic complications, and peripheral neuropathy, related to tissue factor expression and microtubule-inhibiting payload. For trastuzumab  deruxtecan,  the  most  significant  toxicities  are  gastrointestinal  toxicity, myelosuppression, cardiotoxicity, and drug-induced pneumonitis. Trop-2-directed ADCs are more frequently associated with mucositis, myelosuppression, gastrointestinal disorders, and alopecia. The safety profile of each agent is determined not only by the target but also by the type of cytotoxic payload and dosing regimen. Conclusion. ADCs occupy an important position in the treatment of malignancies of the female reproductive system; however, their safe use requires individualized risk assessment, patient education, multidisciplinary monitoring, and timely dose modification. Further research should focus on identifying predictors of toxicity, optimizing preventive measures, and developing personalized ADC regimens.