Coverage Decision for Focinvez (Fosaprepitant) for Trastuzumab Deruxtecan-Induced Nausea and Vomiting
Focinvez (fosaprepitant) should be approved for this patient receiving trastuzumab deruxtecan, as triple antiemetic therapy including an NK1 antagonist is now the recommended standard of care for this agent. 1
Rationale for Coverage
Emetogenic Classification of Trastuzumab Deruxtecan
Trastuzumab deruxtecan contains deruxtecan, a topoisomerase I inhibitor chemotherapy component, which drives its emetogenic potential. 2 While the antibody-drug conjugate is marketed as "targeted therapy," the deruxtecan payload functions as traditional chemotherapy and causes significant nausea and vomiting. 2
Current guidelines now classify trastuzumab deruxtecan as requiring triple antiemetic prophylaxis with mandatory NK1 receptor antagonist administration. 1 The National Comprehensive Cancer Network updated their classification to recognize the high emetic risk of this agent. 1
Evidence Supporting Triple Therapy
A 2023 randomized phase 2 study directly compared doublet therapy (5-HT3 antagonist + dexamethasone) versus triplet therapy (adding NK1 antagonist) for trastuzumab deruxtecan, demonstrating superior complete response rates with triple therapy: 70.0% versus 36.8% (P = 0.0190). 3 This represents a clinically meaningful 33.2% absolute difference in preventing nausea and vomiting. 3
The study investigators concluded that patients receiving trastuzumab deruxtecan require triple therapy with mandatory NK1 receptor antagonist administration. 3
FDA-Approved Indication Met
Fosaprepitant is FDA-approved for prevention of acute and delayed nausea and vomiting associated with moderately emetogenic chemotherapy, which encompasses the deruxtecan component of this antibody-drug conjugate. 4
The FDA label specifically indicates fosaprepitant for prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy in combination with other antiemetic agents. 4
Guideline-Concordant Dosing
The recommended regimen is fosaprepitant 115 mg IV (or 150 mg IV single-dose alternative) on day 1, combined with a 5-HT3 antagonist and dexamethasone 12 mg. 1
Dexamethasone dosing must be reduced to 50% of standard dose (12 mg instead of 24 mg) when combined with aprepitant/fosaprepitant due to CYP3A4 interaction. 1
The 5-HT3 antagonist options include palonosetron 0.25 mg IV, granisetron 1 mg IV, or ondansetron 8-12 mg IV on day 1. 1
Clinical Impact
Without adequate antiemetic prophylaxis, the incidence of chemotherapy-induced nausea and vomiting remains unacceptably high, with delayed CINV occurring in 62.3% of patients and significantly impacting quality of life. 5
NK1 receptor antagonists provide significantly increased protection from delayed emesis and nausea, which is particularly problematic with trastuzumab deruxtecan. 1
Nausea was reported as a grade 3 or higher adverse event in 7.6% of patients receiving trastuzumab deruxtecan in pivotal trials, underscoring the need for optimal antiemetic prophylaxis. 2
Common Pitfalls to Avoid
Do not use doublet therapy alone for trastuzumab deruxtecan. The evidence clearly demonstrates inferior outcomes compared to triple therapy including NK1 antagonist. 3
Do not use full-dose dexamethasone when combining with fosaprepitant. The dose must be reduced by 50% to account for drug-drug interaction via CYP3A4 inhibition. 1
Ensure prophylactic administration 30-60 minutes before chemotherapy rather than waiting for symptoms to develop. 1 Fosaprepitant has not been studied for treatment of established nausea and vomiting. 4