Multidisciplinary Clinical Guidance on Trastuzumab Deruxtecan (T-DXd) –Related Interstitial Lung Disease—Focus on Proactive Monitoring, Diagnosis, and Management

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) composed of an anti-human epidermal growth factor receptor 2 (HER2) humanized monoclonal antibody, a tetrapeptide-based cleavable linker, and a topoisomerase I inhibitor payload. [1] The linker remains stable in plasma and is selectively cleaved by cathepsins that are upregulated in tumor cells. [1-4] The cytotoxic payload is present at an approximately 8:1 drug-to-antibody ratio; is membrane permeable, which potentially results in a bystander effect when it is released from HER2-expressing cells and enters neighboring cells (regardless of HER2 expression); and has a short half-life, minimizing off-target effects (Figure 1).

Source: Cancer Treatment Reviews - March 11, 2022 Category: Cancer & Oncology Authors: Sandra M. Swain, Mizuki Nishino, Lisa H. Lancaster, Bob T. Li, Andrew G. Nicholson, Brian J. Bartholmai, Jarushka Naidoo, Eva Schumacher-Wulf, Kohei Shitara, Junji Tsurutani, Pierfranco Conte, Terufumi Kato, Fabrice Andre, Charles A. Powell Tags: Complications of Treatment Source Type: research