Real-World Data Support T-DXd in HER2-Low mBC in Community Setting

Fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) showed favorable efficacy for patients with HER2-low metastatic breast cancer in the community setting, where patients had a more diverse selection of disease burden and demographics than in the clinical trial setting, according to data presented at the 43rd Annual Miami Breast Cancer Conference.

T-DXd is an established treatment for patients in this population, but limited information exists regarding the efficacy of the treatment in community settings. To address this gap in knowledge, researchers conducted a retrospective analysis of medical records from community settings to gauge who is receiving T-DXd and how they fare after beginning treatment.

Understanding the Real-World Patient Population

The study looked at 300 randomly sampled adult patients with HER2-low mBC. This real-world group appeared to be older, frailer, and more heavily pretreated than typical patients enrolled in clinical trials for T-DXd in this setting. The average age was 63.5 years, and most patients were age 65 or older. About 22.7% of patients had an impaired performance status, and 39.3% had at least 1 other health problem or comorbidity.

Regarding cancer subtype, 77% of the patients had hormone receptor (HR)-positive disease, while 23% had HR-negative disease. About a quarter (24.7%) of patients had metastatic disease at diagnosis.

Treatment Patterns and Sequencing

Most patients (87.3%) received T-DXd as a single therapy rather than in combination with other drugs. There were notable differences in when patients started T-DXd based on hormone receptor status. For those with HR-positive disease, 88.7% received T-DXd as a third or later line of treatment. In contrast, only 53.6% of HR-negative patients received it that late in their treatment journey.

Clinical Efficacy and Survival

Overall, T-DXd showed favorable efficacy in the community setting. On average, patients went more than 7 months before their cancer worsened, and more than half of the patients saw their tumors shrink.

The study measured real-world progression-free survival (PFS). For the whole group, PFS was 7.4 months. When broken down by hormone receptor status, PFS was 7.7 months for HR-positive patients and 4.9 months for HR-negative patients. Additionally, about 62% of all patients were alive 1 year after starting the treatment.

Specific Findings for Subgroups

The research found that certain groups of patients had particularly positive results:

• Patients with HR+ disease who had not received prior chemotherapy for their metastatic cancer did especially well. Chemotherapy-naive patients had a longer time before their cancer worsened (10.2 months) compared to those who had received prior chemotherapy (7.4 months).
• Among the chemotherapy-naive patients with HR-positive disease, 74% were alive at the 1-year mark, and 71% experienced a reduction in tumor size.
• Patients with brain metastases had a PFS of 6.3 months, which was numerically similar to the 7.5 months seen in patients without brain metastases.

Implications for Care

These findings support using T-DXd across a wide range of real-world patients in community cancer settings. Even though the patients in this study were often older or had more health problems than those in highly controlled clinical trials, the therapy still demonstrated favorable efficacy. This suggests that the benefits of T-DXd extend to the diverse types of patients seen in everyday medical practice.

Reference

Nguyen M, Shah R, Gogate A, et al. Trastuzumab deruxtecan in HER2-low metastatic breast cancer: real-world treatment patterns and outcomes from community oncology settings. Poster presented at: 43rd Annual Miami Breast Cancer Conference; March 2026; Miami, FL