Body mass index as a prognostic factor for trastuzumab deruxtecan efficacy in advanced breast cancer: A multicenter retrospective real-world analysis.

Abstract

e13078 Background: Trastuzumab deruxtecan (T-DXd), an antibody–drug conjugate (ADC), has improved outcomes in HER2-positive and HER2-low advanced breast cancer, yet clinical responses remain variable. Body mass index (BMI), a surrogate of systemic metabolic status, may influence therapeutic efficacy, but its prognostic relevance in patients treated with T-DXd remains unclear. Methods: This multicenter, retrospective, real-world study included 199 patients aged ≥ 18 years with advanced HER2-positive or HER2-low breast cancer treated with T-DXd between January 2020 and September 2025 at two centers in China. Patients were stratified according to BMI ( < 24 vs. ≥24 kg/m²) based on guideline-recommended cutoffs for the Chinese population. Propensity score matching (PSM) with a 1:2 ratio was applied to balance baseline characteristics. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). Results: After PSM, 119 patients were analyzed (BMI < 24 kg/m², n = 76; BMI ≥24 kg/m², n = 43), with well-balanced baseline characteristics between groups. At a median follow-up of 10.97 months, median PFS for the overall cohort was 6.40 months (95% CI: 4.60–8.21). On multivariable Cox analysis, BMI ≥24 kg/m² was independently associated with prolonged PFS (HR 0.52, 95% CI: 0.31–0.86, P = 0.011), with median PFS of 8.73 vs. 5.18 months compared with BMI < 24 kg/m². Although differences did not reach statistical significance, patients with BMI ≥24 kg/m² demonstrated numerically higher ORR (37.2% vs. 27.6%, P = 0.278) and DCR (93.0% vs. 85.5%, P = 0.223) than those with BMI < 24 kg/m². Notably, in the subgroup of patients with brain metastases (n = 35), a statistically significant improvement in ORR was observed in the higher BMI group (57.1% vs. 23.8%, P = 0.046), while DCR remained similar between BMI categories (92.9% vs. 90.5%, P = 0.805). Subgroup analyses further indicated that the association between higher BMI and improved PFS was most evident among patients without prior exposure to ADC (HR 0.32, 95% CI: 0.16-0.65, P = 0.002), and a consistent association between higher BMI and longer PFS was also observed in the HER2-low subgroup (HR 0.34, 95% CI: 0.16-0.73, P = 0.006). TRAEs were generally manageable, and no clinically meaningful differences in safety profiles or incidence of grade ≥3 adverse events were observed between BMI groups. Conclusions: This study indicated that a higher BMI (≥24 kg/m²) was independently associated with inproved efficacy in patients with advanced breast cancer treated with T-DXd, particularly among ADC-naïve patients, HER2-low patients, and patients with brain metastases. These findings suggest that BMI could be a valuable factor for prognostic stratification in patients receiving T-DXd.