Clinical Practices and Institutional Protocols on Prophylaxis, Monitoring, and Management of Selected Adverse Events Associated with Trastuzumab Deruxtecan

Abstract

The treatment of metastatic breast cancer (mBC) has evolved significantly in the past several years with the approval of new targeted agents. Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate with a topoisomerase I inhibitor payload, is a new addition to the class of therapies that target the human epidermal growth factor 2 (HER2) receptor. T-DXd was approved in the US in December 2019 for patients with HER2-positive metastatic or unresectable breast cancer who have received 2 or more prior anti-HER2-based regimens in the metastatic setting. In the DESTINY-Breast01 phase II trial (NCT03248492), T-DXd demonstrated high rates of durable responses in heavily pretreated patients with HER2-positive mBC, with a confirmed objective response rate of 62%, median duration of response of 18.2 months, and median progression-free survival of 19.4 months. In addition to efficacy, successful implementation of any new anticancer therapy includes learning how to prevent, monitor, and manage treatment-related adverse events. As T-DXd becomes more widely used, information can be gained from real-world clinical practices, institutional approaches, and the collaboration of multidisciplinary oncology teams who treat patients with T-DXd. This article reviews practical insights and management of nausea and vomiting, neutropenia, interstitial lung disease, risk of cardiotoxicity, and other adverse events associated with T-DXd administration from the perspective of health care providers who have experience utilizing T-DXd.

Keywords: breast neoplasm; clinical practice patterns; drug-related side effects and adverse reactions; trastuzumab deruxtecan.

© The Author(s) 2022. Published by Oxford University Press.

Figures

Figure 1.

Prophylactic and management strategies for nausea and vomiting associated with T-DXd therapy. a5-HT3 receptor antagonist (choose one). • Dolasetron 100 mg PO once. • Granisetron 10 mg SC once or 2 mg PO once or 0.01 mg/kg (max. 1 mg) IV once or 3.1 mg/24-hour transdermal patch applied 24 to 48 hours prior to first dose of T-DXd. • Ondansetron 16 mg to 24 mg PO once or 8 mg to 16 mg IV once. • Palonosetron 0.25 mg IV once. bDexamethasone 12 mg PO/IV once. cMay add NK1R antagonist (choose one). • Aprepitant 125 mg PO once. • Aprepitant injectable emulsion 130 mg IV • Fosaprepitant 150 mg IV once. • Netupitant 300 mg/palonosetron 0.5 mg (available as fixed-combination product only) PO once. • Fosnetupitant 235 mg/palonosetron 0.25 mg (available as fixed-combination product only) IV once. • Rolapitant 180 mg PO once on days 2 and 3. dDexamethasone 12 mg IV. eOndansetron 16 mg IV. fDexamethasone 8 mg PO/IV once on days 2 and 3. g5-HT3 receptor antagonist. • Granisetron 1 mg to 2 mg (total dosage) PO daily or 0.01 mg/kg (max. 1 mg) IV SC once or 2 mg PO once or 0.01 mg/kg (max. 1 mg) IV once on days 2 and 3. • Ondansetron 8 mg PO once (twice daily) or 16 mg PO daily or 8 mg to 16 mg IV daily on days 2 and 3. • Dolasetron 100 mg PO daily on days 2 and 3. hOlanzapine 5 mg to 10 mg PO daily on days 2 and 3. iLorazepam 0.5 mg to 2 mg PO beginning on the night before treatment and repeated the next day 2 hours before anticancer therapy begins to manage anticipatory N/V, or 0.5 mg to 1 mg PO Q6H PRN. Breakthrough N/V options: jProchlorperazine 10 mg IV/PO Q6H PRN for N/V. kDexamethasone 4 mg to 8 mg BID. lOndansetron 8 mg PO every 8 to 12 hours (16 mg-24 mg total daily dosage or 8 mg-16 mg IV). mOlanzapine 2.5 mg to 10 mg PO daily. Abbreviations: BID, twice a day; IV, intravenous; NK1R, neurokinin-1 receptor; N/V, nausea/vomiting; PO, by mouth; PRN, as needed; Q6H, every 6 hours; SC, subcutaneous; T-DXd, trastuzumab deruxtecan.

Figure 2.

ILD associated with T-DXd treatment: patient counseling, pretreatment screening, on-treatment monitoring, and confirmation. Abbreviations: CBC, complete blood count; COPD, chronic obstructive pulmonary disease; CT, computed tomography; ID, infectious disease; ILD, interstitial lung disease; PFT, pulmonary function test; PK, pharmacokinetic; T-DXd, trastuzumab deruxtecan.

Figure 3.

The multidisciplinary approach to preventing, monitoring for, and managing AEs associated with T-DXd therapy. aThe roles of the nurse navigators and triage nurses described here may interchange or overlap, depending on the institution. Abbreviations: AE, adverse event; MDT, multidisciplinary team; NP, nurse practitioner; PA, physician assistant; T-DXd, trastuzumab deruxtecan.