PMID- 38502995 OWN - NLM STAT- MEDLINE DCOM- 20240408 LR - 20240408 IS - 1532-1967 (Electronic) IS - 0305-7372 (Linking) VI - 125 DP - 2024 Apr TI - Clinical management, monitoring, and prophylaxis of adverse events of special interest associated with datopotamab deruxtecan. PG - 102720 LID - S0305-7372(24)00047-1 [pii] LID - 10.1016/j.ctrv.2024.102720 [doi] AB - 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 of cytotoxic agents to tumor cells. Datopotamab deruxtecan (Dato-DXd) is a novel ADC comprising a topoisomerase I inhibitor payload and a monoclonal antibody directed to trophoblast cell-surface antigen 2 (TROP2), a protein that is broadly expressed in several types of solid tumors. Dato-DXd is being investigated across multiple solid tumor indications. In the ongoing, first-in-human TROPION-PanTumor01 phase I study (ClinicalTrials.gov: NCT03401385), encouraging and durable antitumor activity and a manageable safety profile was demonstrated in patients with advanced/metastatic hormone receptor-positive/human epidermal growth factor receptor2-negative breast cancer (HR+/HER2- BC), triple-negative breast cancer (TNBC), and non-small cell lung cancer (NSCLC). Improved understanding of the adverse events (AEs) that are associated with Dato-DXd and their optimal management is essential to ensure safe and successful administration. Interstitial lung disease/pneumonitis, infusion-related reactions, oral mucositis/stomatitis, and ocular surface events have been identified as AEs of special interest (AESIs) for which appropriate prevention, monitoring, and management is essential. This article summarizes the incidence of AESIs among patients with HR+/HER2- BC, TNBC, and NSCLC reported in TROPION-PanTumor01. We report our recommendations for AESI prophylaxis, early detection, and management, using experience gained from treating AESIs that occur with Dato-DXd in clinical trials. CI - Copyright (c) 2024 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Heist, Rebecca S AU - Heist RS AD - Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Harvard University, Boston, MA, USA. Electronic address: rheist@partners.org. FAU - Sands, Jacob AU - Sands J AD - Thoracic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. FAU - Bardia, Aditya AU - Bardia A AD - Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA. FAU - Shimizu, Toshio AU - Shimizu T AD - Department of Pulmonary Medicine and Medical Oncology, Wakayama Medical University Hospital, Wakayama Medical University Graduate School of Medicine, Wakayama, Japan. FAU - Lisberg, Aaron AU - Lisberg A AD - Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA. FAU - Krop, Ian AU - Krop I AD - Yale Cancer Center, New Haven, CT, USA. FAU - Yamamoto, Noboru AU - Yamamoto N AD - Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan. FAU - Kogawa, Takahiro AU - Kogawa T AD - Department of Advanced Medical Development, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. FAU - Al-Hashimi, Saba AU - Al-Hashimi S AD - Department of Ophthalmology, UCLA Stein Eye Institute, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA. FAU - Fung, Simon S M AU - Fung SSM AD - Department of Ophthalmology, UCLA Stein Eye Institute, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA. FAU - Galor, Anat AU - Galor A AD - Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, FL, USA; Research Services, Miami Veterans Affairs Medical Center, Miami, FL, USA. FAU - Pisetzky, Francesca AU - Pisetzky F AD - Clinical Safety and Pharmacovigilence, Daiichi Sankyo, Inc., Schiphol-Rijk, The Netherlands. FAU - Basak, Priyanka AU - Basak P AD - Clinical Safety and Pharmacovigilance, Daiichi Sankyo, Inc., Basking Ridge, NJ, USA. FAU - Lau, Cindy AU - Lau C AD - Clinical Safety and Pharmacovigilance, Daiichi Sankyo, Inc., Basking Ridge, NJ, USA. FAU - Meric-Bernstam, Funda AU - Meric-Bernstam F AD - Department of Investigational Cancer Therapeutics, MD Anderson Cancer Center, University of Texas, Houston, TX, USA. LA - eng SI - ClinicalTrials.gov/NCT03401385 PT - Journal Article PT - Review DEP - 20240311 PL - Netherlands TA - Cancer Treat Rev JT - Cancer treatment reviews JID - 7502030 RN - 0 (Antineoplastic Agents) RN - 0 (Immunoconjugates) RN - P188ANX8CK (Trastuzumab) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - XT3Z54Z28A (Camptothecin) SB - IM MH - Humans MH - Female MH - *Carcinoma, Non-Small-Cell Lung MH - *Triple Negative Breast Neoplasms MH - *Lung Neoplasms MH - *Antineoplastic Agents MH - *Immunoconjugates/adverse effects MH - Trastuzumab MH - *Breast Neoplasms MH - Receptor, ErbB-2 MH - Camptothecin MH - Clinical Trials, Phase I as Topic OTO - NOTNLM OT - (6/6) adverse events OT - Dato-DXd OT - Datopotamab deruxtecan OT - HR+/HER2- breast cancer OT - NSCLC OT - TNBC COIS- Declaration of competing interest The authors have declared all competing financial interests or personal relationships that could have appeared to influence the work reported in this paper above. EDAT- 2024/03/20 00:42 MHDA- 2024/04/08 06:43 CRDT- 2024/03/19 19:01 PHST- 2024/01/25 00:00 [received] PHST- 2024/03/07 00:00 [revised] PHST- 2024/03/10 00:00 [accepted] PHST- 2024/04/08 06:43 [medline] PHST- 2024/03/20 00:42 [pubmed] PHST- 2024/03/19 19:01 [entrez] AID - S0305-7372(24)00047-1 [pii] AID - 10.1016/j.ctrv.2024.102720 [doi] PST - ppublish SO - Cancer Treat Rev. 2024 Apr;125:102720. doi: 10.1016/j.ctrv.2024.102720. Epub 2024 Mar 11.