T-DXd Demonstrates Real-World Efficacy in HER2-Low Metastatic Breast Cancer

To address limited information on community outcomes with the use of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in patients with HER2-low metastatic breast cancer (mBC), researchers conducted a study reviewing medical records from patients treated in community oncology settings, which demonstrated effective outcomes across a range of settings. The analysis was presented at the 43rd Annual Miami Breast Cancer Conference.

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 found in clinical trials. The average age was 63.5 years, and most patients were age 65 or older. Additionally, 22.7% of patients had an impaired performance status, meaning they had more difficulty with daily activities, and 39.3% had at least one other health problem or comorbidity.

Regarding the type of cancer, 77% of the patients had hormone receptor (HR)–positive disease, and 23% had HR-negative disease. Furthermore, 24.7% of patients were diagnosed with de novo metastatic disease.

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 their HR status. For those with HR-positive disease, 88.7% received T-DXd as their third line of treatment or later. In contrast, only 53.6% of HR-negative patients received it that late in their treatment journey.

Clinical Effectiveness and Survival

Overall, T-DXd showed favorable effectiveness in this diverse community setting. For the whole population, the median progression-free survival (PFS) was 7.4 months. When broken down by HR status, it was 7.7 months for those with HR-positive disease and 4.9 months for those with HR-negative disease.

Specific Findings for Subgroups

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

• Patients with HR-positive disease who had not received prior chemotherapy for their metastatic cancer, the median PFS was 10.2 months compared with 7.4 month for those who had received prior chemotherapy.
• Among those with HR-positive disease who were chemotherapy-naive, 74% were alive at the 1-year mark, and 71% experienced reductions in tumor size.
• Patients with brain metastases had a median 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 medicine still demonstrated favorable effectiveness. 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