Abstract Background: Nausea and vomiting (NV) are the most frequent side effects in patients with metastatic breast cancer (MBC) treated with trastuzumab deruxtecan (T-DXd). Since MBC patients may receive T-DXd for an extended period, effective management of NV could help maintain dose intensity, reduce the risk of treatment discontinuation, and improve quality-of-life.Preventing NV can also contribute to reduce other adverse events, like fatigue Effective NV control from the first cycle with a NK1 receptor antagonist (RA)-based regimen is crucial for optimal management throughout subsequent cycles.This exploratory retrospective analysis examined the probability of patients experiencing NV over multiple cycles of T-DXd following antiemetic prophylaxis with NEPA, a fixed-combination of an NK1 RA (netupitant/fosnetupitant) and 5-HT3 RA (palonosetron). Methods: Occurrence and severity of NV in patients with HER2-positive or HER2-low MBC over the first 5 cycles of T-DXd for each patient were extracted and analyzed from clinical records at a single-center in Italy.Probability of NV occurring in each of 5 cycles of T-DXd was estimated using a logistic regression with NV as a dependent variable, cycle as an independent variable and with Generalized Estimating Equation to account for repeated measures. Results: Twenty-five patients were included for a total of 118 cycles. NEPA with dexamethasone was administered as prophylaxis in all but 6 cycles. The median age at T-DXd initiation was 64 years (range, 41-78). The estimated probability of developing NV was low and diminished over each cycle (Table), suggesting that NV was well-controlled with NEPA from the first cycle onward. Conclusion: These exploratory findings indicate that NEPA is likely to be highly effective in preventing NV over multiple cycles in MBC patients receiving T-DXd. It also underscores the value of using an appropriate upfront antiemetic regimen from the first cycle of T-DXd. Citation Format: M. E. Cazzaniga, S. Capici, G. Passarella, F. F. Pepe, T. Clementi, F. Cicchiello, F. Riva, P. Cafaro. Exploratory Analysis of Nausea and Vomiting Probability over Multiple Cycles of NEPA (netupitant/palonosetron) Prophylaxis in Metastatic Breast Cancer Patients Treated withTrastuzumab Deruxtecan abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-05-11.
Cazzaniga et al. (Tue,) studied this question.
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