# Comparing infectious risk of Trastuzumab-deruxtecan to Trastuzumab-emtansine in patients with breast cancer

## TL;DR

This study compares the infection risk of two breast cancer treatments, finding higher infection rates with Trastuzumab-deruxtecan but no significant difference after adjusting for other factors.

## Contribution

The study provides new insights into the infectious risk profile of Trastuzumab-deruxtecan compared to Trastuzumab-emtansine in breast cancer patients.

## Key findings

- Patients treated with T-DXd had a higher incidence of total infections (24.4% vs 14.0%).
- T-DXd was associated with more bloodstream infections and infection-related mortality in unadjusted analysis.
- After adjusting for confounding variables, T-DXd was not significantly linked to increased infection risk.

## Abstract

Trastuzumab-deruxtecan (T-DXd) is an antibody–drug conjugate (ADC) that revolutionized the treatment approach for breast cancer. However, the infectious risk associated with T-DXd is unknown. Here, we evaluate the infectious risk of T-DXd against trastuzumab-emtansine (T-DM1), an ADC with an identical monoclonal antibody.

We conducted a retrospective study of consecutive breast cancer patients who received T-DXd or T-DM1. Demographic data, infection risk factors, infection sites, and opportunistic infections were recorded and compared across treatment groups. Multivariable logistic regression was used to evaluate the association between treatment group and infection, adjusting for clinical risk factors.

374 patients received T-DXd or T-DM1, with 126 receiving T-DXd alone, 196 receiving T-DM1 alone, and 52 patients receiving both treatments. Patients who received T-DXd did so as higher line of therapy (p < 0.001), was given more in the palliative setting (100% vs 33.7%, p < 0.001), had more prior immunosuppressive systemic treatment (78.6% vs 16.9%, p < 0.001), were exposed to more significant corticosteroid courses (17.2% vs 4.5%, p < 0.001), and had more hospitalizations during treatment (57.3% vs 27.7%, p < 0.001). Patients treated with T-DXd had a higher incidence of total infections (24.4% vs 14.0%, p = 0.01); in the infected population, unadjusted analysis reveals that those treated with T-DXd had more bloodstream infections (33.3% vs 5.9%, p = 0.004) and more infection-related mortality (18.2% vs 0%, p = 0.01). Three patients developed opportunistic infections on T-DXd, and 2 of the 3 were treated concurrently with high-dose corticosteroids. For multivariate analysis, after adjustment for clinically relevant variables and those associated with the outcome in univariate analyses, T-DXd was not associated with an increased risk of infection (OR = 1.89, 95% CI: 0.85–4.32, p = 0.12).

Although patients receiving T-DXd had a higher incidence of infection, no significant difference in infectious risk was found after adjusting for several confounding variables. Infection-related mortality and opportunistic infections were rare and only occurred in the T-DXd cohort. Future prospective studies are warranted to more reliably evaluate the infectious risk of T-DXd compared to T-DM1, particularly as T-DXd is increasingly utilized earlier in the treatment course for breast cancer patients.

The online version contains supplementary material available at 10.1007/s10549-026-07937-1.