At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, a study led by Professor Hui Xie from Jiangsu Cancer Hospital was presented as an electronic poster (Abstract e13078). Using multicenter real-world data from China, the study is the first to systematically evaluate the relationship between body mass index (BMI) and the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with HER2-positive or HER2-low advanced breast cancer.The findings showed that patients with BMI ≥24 kg/m² achieved significantly longer median progression-free survival (PFS) than those with lower BMI (8.73 vs. 5.18 months), with particularly pronounced benefits among ADC-naïve patients, those with HER2-low disease, and those with brain metastases. Among patients with brain metastases, the objective response rate (ORR) increased to 57.1% in the higher BMI group compared with 23.8% in patients with BMI <24 kg/m², without an increase in clinically significant toxicity.
These findings suggest that BMI, a simple and readily available clinical measure, may help optimize patient stratification for T-DXd therapy. Oncology Frontier invited Professor Hui Xie to discuss the study.
Study Overview
Study Title
Body Mass Index as a Prognostic Factor for Trastuzumab Deruxtecan Efficacy in Advanced Breast Cancer: A Multicenter Retrospective Real-World Analysis
Background
With its high drug-to-antibody ratio (DAR), bystander antitumor effect, and potent topoisomerase I inhibitor payload, trastuzumab deruxtecan (T-DXd) has become an important treatment option for HER2-positive, HER2-low, and even HER2-ultralow breast cancer.
However, substantial variability in treatment response exists even among patients with similar HER2 expression. Body mass index (BMI), a simple indicator of nutritional status, adipose reserves, and systemic metabolic health, may influence drug distribution, the tumor microenvironment, and treatment tolerance. Its clinical significance in patients receiving T-DXd, however, has remained unclear.
Methods
This retrospective multicenter study included 199 patients with HER2-positive or HER2-low advanced breast cancer treated with T-DXd between January 2020 and September 2025.
Using the Chinese adult BMI classification, patients were divided into:
- Normal weight: BMI <24 kg/m²
- Overweight: BMI ≥24 kg/m²
To minimize baseline confounding, propensity score matching (PSM) was performed, yielding a final analysis cohort of 119 patients.
Following matching, investigators used:
- Kaplan–Meier survival analysis
- Cox proportional hazards regression
to evaluate the association between BMI and progression-free survival (PFS).
Subgroup analyses further examined whether BMI influenced PFS according to:
- HER2 expression
- Previous ADC exposure
- Sites of metastatic disease
The study also assessed:
- Objective response rate (ORR)
- Disease control rate (DCR) in patients with brain metastases
- Treatment-related adverse events across BMI groups
Results
1. Higher BMI Was Independently Associated with Longer PFS
After propensity score matching:
- 76 patients had BMI <24 kg/m²
- 43 patients had BMI ≥24 kg/m²
Baseline clinicopathologic characteristics were well balanced.
After a median follow-up of 10.97 months, median PFS for the overall cohort was 6.40 months.
Patients with BMI ≥24 kg/m² experienced significantly longer median PFS than those with lower BMI:
- 8.73 months vs. 5.18 months
- Log-rank P = 0.019
Multivariable Cox regression confirmed BMI ≥24 kg/m² as an independent predictor of prolonged PFS:
- HR = 0.52
- 95% CI: 0.31–0.86
- P = 0.011
These findings suggest that higher BMI may be associated with greater benefit from T-DXd.
2. The Benefit Was Most Pronounced in HER2-Low and ADC-Naïve Patients
Subgroup analyses demonstrated consistent associations between higher BMI and improved PFS across multiple clinical subgroups.
The greatest benefit was observed among:
- Patients with HER2-low disease
- Patients with no prior ADC therapy
- Patients with no prior trastuzumab treatment
Among ADC-naïve patients, the relationship between higher BMI and improved PFS was particularly significant (P for interaction = 0.014), suggesting that BMI-associated benefit may be most evident in patients receiving their first ADC.
3. Higher BMI Was Associated with Better Intracranial Response
Across the overall population, patients with BMI ≥24 kg/m² showed numerically higher ORR and DCR than those with lower BMI, although these differences were not statistically significant.
Among patients with brain metastases, however:
- ORR was significantly higher in the BMI ≥24 kg/m² group 57.1% vs. 23.8% P = 0.046
Disease control rates remained high in both groups, suggesting that higher BMI may be associated with improved intracranial response to T-DXd.
4. Similar Safety Across BMI Groups
Treatment-related adverse events were generally manageable.
The most common toxicities included:
- Hematologic adverse events
- Gastrointestinal reactions
- Elevated liver enzymes
- Fatigue
No clinically meaningful differences in safety were observed between BMI groups, indicating that the improved efficacy seen among patients with higher BMI was not accompanied by increased toxicity.
Study Conclusions
Among patients with HER2-positive or HER2-low advanced breast cancer receiving T-DXd, BMI ≥24 kg/m² was associated with longer progression-free survival.
The association was particularly evident in:
- HER2-low disease
- Patients without prior trastuzumab exposure
- ADC-naïve patients
Patients with brain metastases and higher BMI also demonstrated superior objective response rates without increased safety concerns.
Overall, BMI represents a simple, inexpensive, and readily available clinical marker that may complement existing predictors when estimating treatment benefit and stratifying patients for T-DXd therapy.
Investigator Perspective
Professor Hui Xie
As T-DXd Use Expands, Better Real-World Patient Stratification Is Needed
The clinical use of T-DXd continues to broaden—from HER2-positive disease to HER2-low and even HER2-ultralow breast cancer.
As eligible patient populations expand, identifying those most likely to benefit has become an increasingly important challenge in routine clinical practice.
While traditional factors such as HER2 expression, hormone receptor status, previous treatments, and metastatic burden remain important, the potential influence of host-related characteristics, including metabolic status, deserves further investigation.
Higher BMI Was Associated with Longer PFS, Particularly in Selected Patient Groups
This study demonstrated that, among Chinese patients with HER2-positive or HER2-low advanced breast cancer, BMI ≥24 kg/m² was independently associated with longer PFS following T-DXd therapy.
The benefit was particularly notable in:
- Patients with HER2-low disease
- Patients receiving ADC therapy for the first time
These findings suggest that host metabolic status may contribute to the heterogeneity of ADC treatment response.
Higher BMI Was Also Linked to Better Intracranial Response
Previous studies have already demonstrated the intracranial activity of T-DXd.
In the present study, patients with brain metastases and higher BMI achieved superior objective response rates, suggesting that BMI may also be associated with increased intracranial sensitivity to T-DXd.
BMI May Become a Practical Clinical Biomarker, Pending Further Validation
Overall, this real-world Chinese multicenter study provides a new perspective on understanding variability in T-DXd efficacy.
Because BMI is easily obtainable in routine clinical practice, it may eventually be incorporated alongside:
- HER2 expression
- Prior treatment history
- Metastatic pattern
- Body composition measurements
to improve treatment prediction and patient stratification.
However, given the retrospective design and relatively small subgroup sample sizes, these findings require confirmation in larger prospective studies involving Chinese patient populations.
Expert Profile
Professor Hui Xie, Jiangsu Cancer Hospital
