Abstract PS1-01-03: Impact of Dexamethasone Premedication Timing on Infusion Reactions in HER2 Positive Breast Cancer

Abstract Background: Infusion reactions (IRs) are frequently observed adverse events associated with HER2-targeted monoclonal antibodies, particularly trastuzumab and pertuzumab. These reactions can impair treatment tolerability and necessitate prolonged observation, delay, or discontinuation of therapy. Although dexamethasone is routinely administered as premedication to mitigate docetaxel-induced hypersensitivity, the optimal timing of dexamethasone administration relative to HER2-targeted therapy remains undefined. This study aimed to evaluate whether administering dexamethasone prior to HER2-targeted agents can reduce the incidence of IRs in patients with HER2-positive early breast cancer receiving standard trastuzumab, pertuzumab, and docetaxel therapy. Methods: This randomized, open-label, multicenter trial enrolled 100 patients with HER2-positive stage I-III breast cancer across multiple institutions. Patients were randomly assigned (1:1) to receive dexamethasone either before (experimental group) or after (control group) the infusion of trastuzumab and pertuzumab during the first treatment cycle. All patients received standard chemotherapy with docetaxel (75 mg/m2), trastuzumab (8 mg/kg loading dose), and pertuzumab (840 mg loading dose). Dexamethasone was administered intravenously at 9.9 mg either immediately prior to HER2-targeted therapy or after completion, according to group assignment. The primary endpoint was the incidence of any-grade IRs during the first cycle. Secondary endpoints included the incidence of grade >=3 IRs, IRs during cycle 2, and overall treatment-related adverse events (AEs). The time of IR onset relative to dexamethasone administration was also analyzed. Results: Of the 100 patients enrolled, 50 were allocated to each group. The incidence of IRs during cycle 1 was significantly lower in the experimental group (24.0%) compared to the control group (60.0%) (p < 0.001), resulting in an absolute risk reduction of 36.0% and a number needed to treat (NNT) of 2.8. No grade >=3 IRs occurred in either group. During cycle 2, IR incidence was low and did not significantly differ between the experimental and control groups (8.0% vs. 10.2%, p = 0.703), suggesting that immune tolerance may develop after initial exposure. The frequency of treatment-related AEs, including hematologic and non-hematologic toxicities, was comparable between groups (98.0% vs. 100.0%; p > 0.999). A time-course analysis showed that most IRs in the control group occurred prior to dexamethasone administration, indicating a potential protective effect of early corticosteroid exposure. Conclusions: Premedication with dexamethasone administered prior to HER2-targeted agents significantly reduced the incidence of IRs during the first treatment cycle without introducing additional toxicity. This simple, cost-effective modification to standard premedication protocols improves the safety and tolerability of trastuzumab and pertuzumab combination therapy. Given the widespread use of monoclonal antibodies in oncology, our findings may have broader implications for optimizing premedication strategies across various therapeutic settings. Citation Format: R. Matsunuma, S. Nakagaki, E. Nakatani, M. Kikuchi, N. Wada, K. Yonezawa, T. Isono, R. Hayami, M. Kaga, M. Tsuneizumi. Impact of Dexamethasone Premedication Timing on Infusion Reactions in HER2 Positive Breast Cancer [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 PS1-01-03.