Impact of antiemetic prophylaxis on reducing trastuzumab deruxtecan dose modifications in HER2+/HER2-low breast cancer

Background: Avoiding unnecessary dose reductions is important for patients with advanced breast cancer (ABC) receiving trastuzumab deruxtecan (T-DXd). Nausea and vomiting, the most common adverse events of T-DXd, frequently necessitate dose reductions, which may impact treatment benefit. Methods: This retrospective exploratory study investigated the impact of triple antiemetic regimen (TAR) prophylaxis on T-DXd dose preservation over time. Data from 143 human epidermal growth factor receptor 2 (HER2)-positive or HER2-low ABC patients who received ≥2 T-DXd cycles were stratified based on TAR use in the first cycle. TAR included an NK₁ receptor antagonist, a 5-HT₃ receptor antagonist (or fixed netupitant/palonosetron combination), and dexamethasone. Results: Patients receiving TAR in the first cycle were significantly less likely to require T-DXd dose reductions in subsequent cycles than the non-TAR group (31.3% vs. 66.7%, P = 0.033). The lowest T-DXd dose relative to initial dose for each patient was significantly higher in the TAR group than in the non-TAR group (100% vs. 80.6%, P = 0.001). There was a trend toward a longer median time to T-DXd dose reduction in the TAR group (15.7 vs. 3.9 months; P = 0.183). Conclusion: These findings suggest that upfront TAR may help maintain the dosing of T-DXd in patients with HER2-positive or HER2-low ABC.