Management of Chemotherapy-Induced Nausea and Vomiting with Trastuzumab Deruxtecan: A Case Series

Abstract

<b><i>Introduction:</i></b> Trastuzumab deruxtecan is a monoclonal antibody linked to a chemotherapy moiety that was recently approved by the Food and Drug Administration (FDA) for the treatment of metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancers. There are labeled black box warnings for interstitial lung disease (ILD)/pneumonitis and embryo-fetal toxicity. Additionally, chemotherapy-induced nausea and vomiting (CINV) was reported to be as high as 78% (∼8% grade 3 or higher) in phase I and II clinical trials. Clinical trial and package insert recommendations for the management of CINV are not available, making real-world management difficult. <b><i>Case Presentation:</i></b> We reviewed the first 10 patients who received trastuzumab deruxtecan at our hospital-based community cancer center to determine if CINV management was adequate. We found a rate of 28.9% CINV (all grade 1 and 2) despite treatment as a moderate emetic potential regimen. Interventions by the treatment team to manage trastuzumab deruxtecan as a high-risk emetic regimen resulted in reduced CINV and ongoing treatment for all patients. <b><i>Discussion and Conclusion:</i></b> This review indicates that management of CINV for patients receiving trastuzumab deruxtecan should follow recommendations for regimens with a high-risk emetic potential.

Optimizing treatment management of trastuzumab deruxtecan in clinical practice of breast cancer

“…When intervention was amended to the high-risk protocol (premedication using 130 mg aprepitant, 12 mg dexamethasone, and 16 mg ondansetron and take-home prescriptions of dexamethasone, ondansetron, and olanzapine), no instances of T-DXd-related nausea and vomiting were reported in the two patients treated (0 of 3 doses). 40 If we took the approach of treating all patients receiving T-DXd using the high-emetic-risk protocol, it is expected that most would respond well, but a percentage of patients could possibly be overmedicated who also could have responded well to the moderate-emetic-risk protocol. Additionally, in our experience, even with treatment using the high-emetic-risk regimen, there may still be patients who do not respond well.…”

Management of Trastuzumab Deruxtecan-related nausea and vomiting in real-world practice

“…Based on early clinical trial data, T-DXd was previously categorized as moderately emetogenic ( 11 , 12 ). However, with the maturation of real-world experience suggesting an inadequate nausea control with the two-drug prophylaxis in a non-negligible proportion of patients ( 13 , 14 ), in January 2023, the NCCN guidelines re-categorized T-DXd as a highly emetogenic agent, modifying the recommendation to endorse a three-drug antiemetic regimen for all patients ( 15 ). In January 2024, the ESMO guidelines have incorporated explicit recommendations for the management of T-DXd-related nausea and vomiting, categorizing it as a pharmaceutical agent at the high end of the moderate category ( 16 ).…”

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

“…1 ), which has resulted in reduced N/V. 19 The standard breakthrough/as needed medications (eg, prochlorperazine, dexamethasone, ondansetron, olanzapine; see Fig. 1 ) are still used at home for breakthrough symptoms but are needed less frequently given the adjusted antiemetic premedication regimen.…”