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

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. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-023-01328-x.

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“…Depending on the severity of this adverse effect, the treatment may need to be discontinued. Proper optimization of the treatment and the adverse effect management are required for maximal benefit [ 58 , 59 ]. Although most ADCs, such as trastuzumab-duocarmazine, MM-302, and RC48-ADC, are based on targeting HER2, researchers are also exploring other ADCs like ladiratuzumab-vedotin and cofetuzumab-pelidotin by selecting TNBC-expressing LIV1 and PI3K as molecular targets, respectively [ 26 ].…”