1539 Background: HER2-low disease has recently emerged as a distinct, targetable category in metastatic breast cancer (MBC), with trastuzumab deruxtecan (T-DXd) demonstrating a clinically meaningful overall survival (OS) benefit. In Brazil, however, access to innovative oncology therapies within the Unified Health System (SUS) is frequently delayed. We quantified the population-level consequences of delayed access to T-DXd for patients with HER2-low MBC. Methods: We conducted a nationwide population-impact analysis from the public-payer perspective, combining Brazilian epidemiologic data with survival benefit estimates derived from randomized clinical trials, using an exponential approximation to model long-term outcomes under delayed-access scenarios. An annual eligible cohort was constructed stepwise from incident MBC (21,133/year), applying: SUS dependence (proxy: 1 - private coverage, p=0.759), HER2-low prevalence (p=0.320), HR+ proportion among HER2-low (proxy using luminal status, p=0.747), and probability of reaching the eligible line of therapy (p line=0.50). Treatment effect inputs were taken from the DESTINY-Breast04 HR+ subgroup (median OS 23.9 vs 17.5 months. OS HR=0.64 95% CI 0.48–0.86). Primary outcome was preventable deaths/year, computed as treated/year × (1 − HR), where treated/year equals the annual eligible cohort multiplied by uptake (95%, 75%, 50%). A sensitivity range for preventable deaths was generated by varying HR across its trial-reported 95% CI. Life-years gained over 10 years were estimated as treated/year × 10 × Δmedian OS (years). One-way sensitivity varied p (HER2-low) from 0.25 - 0.46 (uptake fixed at 95%). Results: The modeled annual eligible cohort was 1,917 patients/year, treated/year was 1,821 (95% uptake), 1,438 (75%), and 959 (50%). Estimated preventable deaths/year were 656 (range 255-947), 518 (201-748), and 345 (134-498), corresponding to 6,560, 5,180, and 3,450 deaths avoided over 10 years, respectively. Life-years gained over 10 years were 9,713, 7,668, and 5,112 across the three uptake scenarios. Varying p(HER2-low) from 0.25-0.46 yielded 513-943 preventable deaths/year and 7,588-13,962 life-years gained (10 years) at 95% uptake. Conclusions: Delayed access to T-DXd within Brazil’s public health system may result in substantial, avoidable mortality among patients with HER2-low MBC. These findings highlight the urgent need for accelerated incorporation pathways, consistent HER2-low testing, and operational readiness to translate proven survival gains into real-world benefit. Scenario Uptake Treated/year Preventable deaths/year Range (HR 95% CI) Life-years gained (10 years) Base-case (95%) 95.0% 1,821 656 255 – 947 9,713 Moderate (75%) 75.0% 1,438 518 201 – 748 7,668 Conservative (50%) 50.0% 959 345 134 – 498 5,112
Yabrude et al. (Wed,) studied this question.