Abstract Background: Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody drug conjugate approved for the treatment of HER2-positive (HER2+) and HER2-low metastatic breast cancer (mBC). Currently, there is limited evidence assessing how T-DXd is used in a Canadian real-world (RW) setting. The aim of this observational study was to describe RW treatment-related outcomes using data collected from patients with HER2+ mBC who enrolled in AstraZeneca Canada’s patient support program (PSP) for treatment with T-DXd, following regulatory approval based on the DESTINY-Breast03 (DB-03) trial. Methods: This interim analysis included all patients enrolled in the PSP from June 2022 to August 2023 and initiated T-DXd therapy. The index date was the date of treatment initiation with follow-up until treatment discontinuation or close of the PSP. Primary objectives included rates of treatment discontinuation and dose modifications (dose reduction or discontinuation or dose interruptions 1 cycle length). Secondary objectives included time to treatment discontinuation (TTD), reasons for discontinuation (reported by physicians), and duration of treatment (excluding cumulative length of dose interruptions). Time-to-event outcomes were analyzed using the Kaplan-Meier method; other outcomes were summarized descriptively. Results: A total of 347 patients were included with a mean age of 60 years (SD, 13.2); 6% (n=19) had no prior lines of therapy in the metastatic setting, 64% (n=222) had 1, 9% (n=30) had 2, and 4% (n=14) had 3+, with 18% (n=62) missing data; 30% (n=103) had stable brain metastases at enrollment. Median follow-up was 5.6 months (range 0.2-29.7). Among patients that started at a dose of 5.4 mg/kg (84.4%, n=293) or a lower dose of 4.4 or 3.2 mg/kg (n=20, 5.8%), 32% (n=101) had a dose reduction, 28% (n=87) had a discontinuation, 51% (n=161) had either a dose reduction or discontinuation, and 51% (n=161) had a dose interruption. Some patients (n=34, 9.8%) received a dose not specified in the label (neither 5.4, 4.4, or 3.2 mg/kg). Cumulative probabilities of treatment discontinuation at 3, 6 and 9 months were 10.2% (95% CI, 6.8-13.4), 18.2% (95% CI, 13.6-22.6), and 29.7% (95% CI, 23.3-35.6), respectively. Overall median TTD was 14.3 months (95% CI, 12.4-18.4); median TTD among patients with stable brain metastases was 15.2 months (95% CI, 15.2-not reached). Median duration of treatment (excluding dose interruptions) was 12.7 months (95% CI, 10.3-18.4). Of the total observed discontinuations (28%, n=98) progression was the most common reason (44%, n=43) followed by prescriber decision (23%, n=22), death (16%, n=15), patient decision (12%, n=12), or other/unknown/missing data (6%, n=6). Conclusion: RW use of T-DXd in the Canadian PSP, designed for patients eligible under the regulatory authorization based on DB-03, reflected a largely second-line setting, with a median TTD consistent across the overall population and patients with stable brain metastases. Due to the short duration of follow-up, TTD may be underestimated. During the PSP enrollment period, T-DXd use was still in its early stage of experience in Canada and as such, understanding of optimal therapy management may have still been evolving. Citation Format: C. Brezden-Masley, S. Shokar, A. Nam, R. A. Qadeer, Z. Senhaji Mouhri, B. Salvo, N. Bonar, B. Suero. Interim results: Real world study of treatment discontinuations and modifications for patients with HER2-positive metastatic breast cancer on trastuzumab deruxtecan on a Canadian patient support program 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 PS5-04-02.
Brezden‐Masley et al. (Tue,) studied this question.