Antiemetic Therapy for Trastuzumab Deruxtecan-Induced Nausea and Vomiting

Emetogenic Classification and Evidence

The addition of NK1 antagonists to standard therapy provides significantly increased protection from delayed emesis and nausea in patients receiving emetogenic chemotherapy, as recommended by the National Comprehensive Cancer Network 1
Fosaprepitant is FDA-approved for prevention of acute and delayed nausea and vomiting associated with highly emetogenic chemotherapy, as well as prevention of delayed nausea and vomiting associated with moderately emetogenic chemotherapy 2, 1

The American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend fosaprepitant 115 mg IV (or 150 mg IV single-dose alternative) on day 1, as part of triple antiemetic therapy for patients receiving trastuzumab deruxtecan 2, 1, 3
Dexamethasone 12 mg PO or IV is recommended on day 1, with a reduced dose due to aprepitant interaction via CYP3A4, as suggested by the European Society for Medical Oncology 4, 3
A 5-HT3 antagonist, such as palonosetron 0.25 mg IV, granisetron 1 mg IV, or ondansetron 8-12 mg IV, is recommended on day 1, as part of triple antiemetic therapy for patients receiving trastuzumab deruxtecan 5, 6, 3

Aprepitant/fosaprepitant is a CYP3A4 substrate, moderate inducer, and moderate inhibitor, and may interact with other medications, as noted by the National Comprehensive Cancer Network 2, 1
The dose of dexamethasone should be reduced to 50% when combining with aprepitant, due to CYP3A4 interaction, as recommended by the European Society for Medical Oncology 4, 3
Prophylactic administration of antiemetics 30-60 minutes before chemotherapy is recommended, rather than waiting for symptoms to develop, as suggested by the American Society of Clinical Oncology 7, 3