Clinical Guidance on the Monitoring and Management of Trastuzumab Deruxtecan (T-DXd)-Related Adverse Events: Insights from an Asia-Pacific Multidisciplinary Panel

Joanne Wing Yan Chiu (), Soo Chin Lee (), James Chung-man Ho (), Yeon Hee Park (), Ta-Chung Chao (), Sung-Bae Kim (), Elgene Lim (), Ching-Hung Lin (), Sherene Loi (), Su Ying Low (), Lynette Li San Teo (), Winnie Yeo () and Rebecca Dent ()
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Joanne Wing Yan Chiu: The University of Hong Kong
Soo Chin Lee: National University Health System
James Chung-man Ho: The University of Hong Kong
Yeon Hee Park: Sungkyunkwan University School of Medicine
Ta-Chung Chao: National Yang Ming Chiao Tung University
Sung-Bae Kim: University of Ulsan College of Medicine
Elgene Lim: University of New South Wales
Ching-Hung Lin: National Taiwan University Hospital
Sherene Loi: Peter MacCallum Cancer Centre
Su Ying Low: Singapore General Hospital
Lynette Li San Teo: National University Hospital
Winnie Yeo: The Chinese University of Hong Kong
Rebecca Dent: National Cancer Centre Singapore

Drug Safety, 2023, vol. 46, issue 10, No 2, 927-949

Abstract: Abstract Trastuzumab deruxtecan (T-DXd)—an antibody–drug conjugate targeting the human epidermal growth factor receptor 2 (HER2)—improved outcomes of patients with HER2-positive and HER2-low metastatic breast cancer. Guidance on monitoring and managing T-DXd–related adverse events (AEs) is an emerging unmet need as translating clinical trial experience into real-world practice may be difficult due to practical and cultural considerations and differences in health care infrastructure. Thus, 13 experts including oncologists, pulmonologists and a radiologist from the Asia-Pacific region gathered to provide recommendations for T-DXd–related AE monitoring and management by using the latest evidence from the DESTINY-Breast trials, our own clinical trial experience and loco-regional health care considerations. While subgroup analysis of Asian (excluding Japanese) versus overall population in the DESTINY-Breast03 uncovered no major differences in the AE profile, we concluded that proactive monitoring and management are essential in maximising the benefits with T-DXd. As interstitial lung disease (ILD)/pneumonitis is a serious AE, patients should undergo regular computed tomography scans, but the frequency may have to account for the median time of ILD/pneumonitis onset and access. Trastuzumab deruxtecan appears to be a highly emetic regimen, and prophylaxis with serotonin receptor antagonists and dexamethasone (with or without neurokinin-1 receptor antagonist) should be considered. Health care professionals should be vigilant for treatable causes of fatigue, and patients should be encouraged to use support groups and practice low-intensity exercises. To increase treatment acceptance, patients should be made aware of alopecia risk prior to starting T-DXd. Detailed monitoring and management recommendations for T-DXd–related AEs are discussed further.

Date: 2023
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DOI: 10.1007/s40264-023-01328-x

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