Abstract Background: Trastuzumab deruxtecan (T-DXd) is a HER2-directed antibody-drug conjugate approved for HER2+, HER2-low, and HER2-ultralow metastatic breast cancer (mBC) in the United States (US). In January 2023, T-DXd was re-classified as highly emetogenic by the US National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for antiemesis with a recommendation to use a triplet/quadruplet anti-emetic drug (AED) regimen as prophylaxis at treatment initiation to prevent therapy induced nausea and vomiting. However, real-world use of AED prophylaxis among patients initiating T-DXd and the characteristics of those who receive such therapy remains unclear. Methods: This retrospective study analyzed IQVIA PharMetrics Plus® health claims data between 1 January 2019 and 30 September 2024. Included were adult (≥18 years) patients with mBC who initiated T-DXd (index date) between 1 January 2020 and 1 April 2024, had 12 months of continuous data before index (baseline), and no other primary cancer at baseline. Due to a lack of biomarker information in claims data, treatment-based proxies were used to classify HER2 status. HER2+ status was deemed “plausible” if patients initiated T-DXd before August 2022 or had another HER2-targeted therapy prior to T-DXd. Alternatively, HER2-low status was assigned. The number of guideline-recommended AED classes initiated within 3 days before or on index date was used to categorize patients by prophylaxis group (none; mono; dual; triplet/quadruplet regimen). Patient characteristics were described using summary statistics as percentages for categorical variables and as means (or medians) for continuous variables. Results: Of 1,024 patients initiating T-DXd (mean standard deviation age: 59 12 years; 56% HER2+), 31% had triplet/quadruplet, 51% had dual, 9% had mono, and 8% had no AED. Among patients with any AED prophylaxis use, 83% had 5-hydroxytryptamine type 3 antagonist (5-HT3a) + dexamethasone ± neurokinin 1 (NK1) receptor antagonist. From 1 January 2022 to 1 April 2024, the annual prevalence of triplet/quadruplet regimens increased from 19% to 70%, dual regimens decreased from 63% to 19%, mono regimens decreased from 10% to 4%, and no AED prophylaxis remained constant at 7%. Relative to patients with any AED regimen, those with no prophylaxis were older (mean age: 63 12 years vs. 59 12 years), used prior AEDs less frequently before the index prophylaxis window (77% vs. 90%), had a higher proportion with National Cancer Institute comorbidity index score 0 (48% vs 42%) and a lower proportion with brain metastasis (9% vs. 27%). No difference in patient characteristics was observed between patients with mono, dual, or triplet/quadruplet regimens. Triplet/quadruplet AED prophylaxis was used in 24% of the HER2+ subgroup (1 January 2020-1 April 2024) and 41% of the HER2-low subgroup (1 January 2022-1 April 2024). In the first 3 months of 2024, 63% of HER2+ patients and 74% of HER2-low patients were on triplet/quadruplet AED prophylaxis. Conclusion: While patients without AED prophylaxis were older, and had higher comorbidity burden, than patients with any prophylaxis, there were no differences in patient baseline characteristics among patients with mono, dual, or triplet/quadruplet AED prophylaxis. Guidelines are increasingly being followed in the US as demonstrated by the increased use of triplet/quadruplet AED prophylaxis among patients who initiated T-DXd after January 2023, with 5-HT3 antagonist+dexamethasone±NK1 receptor antagonist being the favored regimen. However, of 69 patients in the first 3 months of 2024, 7% of patients still had no AED prophylaxis, and 23% had mono/dual AED prophylaxis, indicating room for education for improvement of guideline implementation. Citation Format: C. H. Shah, C. Nordon, E. Langford, X. Zhao, B. Adeyemi, E. John, A. M. Near, H. Moore. Trends in the Utilization of Prophylactic Anti-Emetic Therapy among Patients Initiating trastuzumab deruxtecan for Metastatic Breast Cancer in the United States 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 PS1-05-15.
Shah et al. (Tue,) studied this question.