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.

Fig. 1

Graphical summary of the Asia-Pacific multidisciplinary panel recommendations for the monitoring and management of T-DXd–related adverse events in patients with metastatic breast cancer. ^aSigns and symptoms of ILD/pneumonitis may include cough, dyspnoea, fever and other new or worsening respiratory symptoms. ^bJunior doctors and breast care nurses may also be included. ^c6-min walk test or 1-minute sit-to-stand tests. ^dComplete workup is recommended upon signs and symptoms of anaemia. ^eSuch as anaemia. ^fSuch as echocardiography and other laboratory tests. 5-HT3 serotonin receptor antagonists CBC complete blood count, CT computed tomography, DEX dexamethasone, G-CSF granulocyte colony-stimulating factor, HRCT high-resolution computed tomography, ILD interstitial lung disease, IV intravenous, LVEF left ventricular ejection fraction, NK1 neurokinin 1 antagonists, PI prescribing information, RBC red blood cell, SpO₂ Oxygen saturation measured by pulse oximetry, T-DXd trastuzumab deruxtecan

Fig. 2

Summary of the Asia-Pacific multidisciplinary panel recommendations for the monitoring and management of T-DXd–related ILD/pneumonitis. The Managing ILD/pneumonitis section of this figure has been adapted from Fig. 3 of Swain SM et al 2021 [28]. ^aOther tests cited by guidelines and clinical trial protocol include blood culture and CBC, PFTs and pulse oximetry, arterial blood gases, PK analysis of blood sample (as clinically indicated and feasible) [28]. BAL bronchoalveolar lavage, CBC complete blood count, CMV cytomegalovirus, CT computed tomography, HRCT high-resolution computed tomography, ILD interstitial lung disease, IV intravenous, MDT multidisciplinary team, PFT pulmonary function test, PK pharmacokinetic, T-DXd trastuzumab deruxtecan