P097 Cutaneous toxicity of antibody–drug conjugates: a real-world cohort of 503 patients across 15 agents

Abstract

The number of antibody–drug conjugates (ADCs) utilized in cancer treatment has expanded rapidly in recent years. Although cutaneous adverse events have been reported in clinical trials, real-world data describing their incidence, severity and clinical impact remain limited. We aimed to describe the incidence, patterns, severity, management and treatment impact of toxicity from ADCs. We conducted a retrospective cohort study using electronic medical records, including all patients receiving ADC therapy at a tertiary cancer hospital between March 2023 and September 2025. Outcomes included the incidence of cutaneous toxicity (graded using the CTCAE criteria), management strategies and the impact on oncological treatment delivery. Analyses were descriptive. In total 503 patients (mean age 58 years) received ADC therapy, including trastuzumab deruxtecan (n = 117), sacituzumab govitecan (n = 76), polatuzumab vedotin (n = 69) and 12 other agents (n = 241). Malignancies treated included breast cancer (51%), lymphomas (38%) and other malignancies (11%). Overall, 145 patients developed cutaneous toxicity, with marked agent-specific variability (0–100%). Among adequately powered cohorts, the incidence of toxicity ranged from 4.3% with belantamab mafodotin to 40.8% with sacituzumab govitecan. ADCs administered in combination with immune checkpoint inhibitors demonstrated the highest rates. Mertansine (DM1)-based ADCs showed consistently low toxicity (11.9%), whereas monomethyl auristatin E-based agents demonstrated wide variability, suggesting influences beyond payload class alone. Common manifestations included oral mucosal ulceration (8.0%) and mucosal inflammation (6.5%). Most graded events were mild (grade 1–2, 94.8%), with grade ≥ 3 toxicity uncommon (5.2%). Treatment interruption occurred in five patients (1.0%); no treatment cessations were attributed to cutaneous toxicity. We report, to our knowledge, the largest real-world cohort to date examining ADC-associated cutaneous toxicity. Approximately one-quarter of patients developed cutaneous adverse events, showing pronounced agent-specific variation, and these were predominantly mild. Importantly, cancer treatment delivery was rarely compromised. These findings highlight marked differences in cutaneous toxicity between ADC agents and support tailored dermatological monitoring as ADC use becomes more widespread.