A single-center retrospective analysis of antibody-drug conjugate utilization and associated toxicities in patients with solid tumors.

Abstract

e15025 Background: Antibody-drug conjugates (ADCs) are increasingly used to treat both hematologic and solid malignancies. Although designed to minimize off-target toxicity, ADCs have demonstrated a more complex adverse event profile than initially anticipated. Despite their expanding use, real-world data describing ADC utilization patterns and toxicities remain limited. Methods: We retrospectively reviewed 678 patients who were treated with one or more ADC at the Brown University Health Cancer Institute from 2015 to 2025. Among these patients, 339 received an ADC for a solid tumor. As some patients received more than one ADC, a total of 375 unique ADC exposures were recorded. Data abstracted from electronic medical records included patient demographics, malignancy type, ADC type, and presence and type of ADC-related toxicities. Toxicity rates were calculated per unique ADC exposure with 95% confidence intervals using the Clopper-Pearson method. Additional analyses were descriptive. Results: The cohort was predominantly female (231/339, 68.1%), reflecting high ADC utilization in treatment of breast cancer (156/339, 46.0%). Other treated malignancies included urothelial (122/339, 36.0%), gastroesophageal (21/339, 6.2%), gynecologic (17/339, 5%), lung (13/339, 3.8%), cholangiocarcinoma, colorectal, and head and neck (each 3/339, 0.9%), and testicular (1/339, 0.3%) cancers. ADC-related toxicities occurred in 20.5% (77/375) of exposures. The most common toxicities were gastrointestinal (25/77, 32.5%), neurologic (20/77, 26.0%), cutaneous (16/77, 20.8%), and pulmonary and hematologic (each 14/77, 18.2%). Less common toxicities included ocular and cardiac (each 2/77, 2.6%) and renal and endocrine (each 1/77, 1.3%). Toxicity rates were similar among the most frequently used ADCs (Enfortumab vedotin, Trastuzumab deruxtecan, and Ado-trastuzumab emtansine), ranging from 17.8% to 23.7%, whereas less frequently administered agents had wide confidence intervals due to small sample sizes. Corresponding data are shown in the table below. Conclusions: In this single-center analysis, ADC-related toxicities occurred in roughly one-fifth of exposures, with comparable rates among commonly used agents and greater variability among less frequently administered ADCs. These findings provide real-world insight into ADC safety and highlight the need for further studies to better define toxicity patterns and guide management. ADC ADC Exposures, N (%) Exposures with Toxicity, N (%) 95% CI, % Enfortumab vedotin 118 (31.5) 28 (23.7) 16.4 - 32.4 Trastuzumab deruxtecan 118 (31.5) 21 (17.8) 11.4 - 25.9 Ado-trastuzumab emtansine 98 (26.1) 21 (21.4) 13.8 - 30.9 Sacituzumab govitecan 28 (7.5) 3 (10.7) 2.3 - 28.2 Mirvetuximab soravtansine 11 (2.9) 3 (27.3) 6.0 - 61.0 Tisotumab vedotin 2 (0.5) 1 (50.0) 1.3 - 98.7 Overall 375 (100) 77 (20.5) 16.6 - 25.0