Safety of antibody-drug conjugates in gynecologic cancers: current evidence and management approaches.

Abstract

Antibody-drug conjugates (ADCs) have emerged as a contemporary targeted therapeutic in gynecologic malignancies, offering novel precision therapy options by linking monoclonal antibodies that target tumor-associated antigens with potent cytotoxic payloads. Several ADCs have demonstrated promising activity in ovarian, endometrial, and cervical cancers, particularly in the recurrent setting. Clinical development has expanded across tumor types and biomarker-defined populations, with ongoing trials exploring ADCs as monotherapy and in combination with immune checkpoint inhibitors, chemotherapy, and antiangiogenics. As ADCs are incorporated as standard-of-care options, understanding their unique adverse event profiles and their management becomes critical. Toxicities are largely influenced by the ADC's structural components, yet most represent off-target toxicities of the cytotoxic payload. Commonly reported adverse events include ocular and gastrointestinal toxicity, hematologic suppression, peripheral neuropathy, and pneumonitis, with type, severity, and onset varying between agents. For instance, tissue-specific toxicities such as keratopathy are prominent with tubulin-directed payloads, while diarrhea and neutropenia are more commonly associated with topoisomerase I inhibitor payloads. Unlike traditional chemotherapy, ADC-associated toxicities often follow a different timeline and may require novel prophylactic and mitigation strategies, including multidisciplinary supportive care. As clinical use of ADCs expands, a thorough understanding of agent-specific toxicities and their management is essential for optimizing therapeutic outcomes. Here, we provide a comprehensive overview of the evolving ADC pipeline in gynecologic cancers, with a particular focus on toxicity patterns, underlying mechanisms, and evidence-based management strategies to support safe and effective integration into routine oncology practice.