Abstract PS2-06-08: Interim results: Real world study of treatment discontinuations and modifications for patients with HER2-low metastatic breast cancer on trastuzumab deruxtecan on a Canadian patient support program

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Abstract Background: Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody drug conjugate approved for the treatment of 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-low mBC who enrolled in AstraZeneca Canada’s patient support program (PSP) following regulatory approval based on the DESTINY-Breast04 (DB-04) trial, and who were among the earliest HER2-low mBC recipients of T-DXd in Canada. Methods: This interim analysis included patients who enrolled in the PSP from January 2023 to March 2024 and initiated T-DXd therapy. 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 860 patients were included with a mean age of 61.8 years (standard deviation [SD], 11.3; range, 29-94); 1.3% (n = 11) had no prior lines of chemotherapy in the metastatic setting, 40% (n = 345) had 1, 27% (n = 233) had 2, and 31% (n = 270) had 3+; 93% (n = 793) were hormone receptor-positive (HR+) and 7% (n = 63) were hormone receptor-negative (HR-). Median follow-up was 4.6 months (range 0.2-22.8). Among patients that started at a dose of 5.4 mg/kg (77.9%, n = 670), 4.4 mg/kg (9.8%, n = 84), or 3.2 mg/kg (1.4%, n = 12), 28% (n = 212) had a dose reduction, 54% (n = 417) had a discontinuation, 67% (n = 516) had a dose reduction or discontinuation, and 54% (n = 410) had a dose interruption. Some patients (n = 94, 10.9%) received a dose not specified in the label (neither 5.4, 4.4, or 3.2 mg/kg). The cumulative probabilities of treatment discontinuation at 3, 6 and 9 months were 21.7% (95% confidence interval [CI], 18.8-24.5), 44.1% (95% CI, 40.3-47.6), and 60.0% (95% CI, 55.8-63.8), respectively. Median overall TTD was 6.9 months (95% CI, 6.2-7.9); median TTD was 7.3 months (95% CI, 6.7-8.2) among HR+ patients and 3.4 months (95% CI, 3.2-4.6) among HR- patients. Median duration of treatment (excluding dose interruptions) was 6.3 months (95% CI, 5.6-7.1). Of the total observed discontinuation (54%, n = 462), progression was the most common reason (52%, n = 241) followed by prescriber decision (16%, n = 73), death (15%, n = 68), patient decision (6.3%, n = 29), adverse event (3.5%, n=16), other (2.6%, n = 12), or unknown/missing data (5.0%, n = 23). Conclusion: Early RW use of T-DXd in the Canadian PSP, designed for patients eligible under the regulatory authorization based on DB-04, reflected treatment patterns in a more heavily pretreated population. 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-low 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 PS2-06-08.

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