Clinical management, monitoring, and prophylaxis of adverse events of special interest associated with datopotamab deruxtecan

• DOI: 10.1016/j.ctrv.2024.102720
• Publication Date: 2024-03-11T17:15:44Z
• Authors: Rebecca S. Heist; Jacob Sands; Aditya Bardia; Toshio Shimizu; Aaron Lisberg; Ian Krop; Noboru Yamamoto; Takahiro Kogawa; Saba Al-Hashimi; Simon S.M. Fung; Anat Galor; Francesca Pisetzky; Priyanka Basak; Cindy Lau; Funda Meric-Bernstam
• Keywords: Lung Neoplasms; Immunoconjugates; Clinical Trials, Phase I as Topic; Receptor, ErbB-2; Carcinoma, Non-Small-Cell Lung; Humans; Female; Triple Negative Breast Neoplasms; Antineoplastic Agents; Breast Neoplasms; Camptothecin; Trastuzumab

Antibody drug conjugates (ADCs) are an emerging class of treatments designed to improve efficacy and decrease toxicity compared with other systemic therapies through the selective delivery cytotoxic agents tumor cells. Datopotamab deruxtecan (Dato-DXd) is a novel ADC comprising topoisomerase I inhibitor payload monoclonal antibody directed trophoblast cell-surface antigen 2 (TROP2), protein that broadly expressed in several types solid tumors. Dato-DXd being investigated across multiple indications. In ongoing, first-in-human TROPION-PanTumor01 phase study (ClinicalTrials.gov: NCT03401385), encouraging durable antitumor activity manageable safety profile was demonstrated patients advanced/metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (HR+/HER2– BC), triple-negative (TNBC), non-small cell lung (NSCLC). Improved understanding adverse events (AEs) associated their optimal management essential ensure safe successful administration. Interstitial disease/pneumonitis, infusion-related reactions, oral mucositis/stomatitis, ocular surface have been identified as AEs special interest (AESIs) for which appropriate prevention, monitoring, essential. This article summarizes incidence AESIs among HR+/HER2 − BC, TNBC, NSCLC reported TROPION-PanTumor01. We report our recommendations AESI prophylaxis, early detection, management, using experience gained from treating occur clinical trials.