Beyond the Trial Population: Real-World Outcomes With T-DXd in HER2-Low Metastatic Breast Cancer

Patients selected for enrollment in clinical trials often have very narrow inclusion criteria. Once clinical trials show the efficacy of a new treatment, only then is the treatment option available to a more diverse patient population.

Similar findings have now been observed with fam-trastuzumab deruxtecan-nxki (T-DXd) in patients with HER2-low metastatic breast cancer (mBC). A real-world analysis of patients treated in community oncology settings revealed that T-DXd maintained clinical benefit even among older patients and those with more medically complex conditions. The findings were presented in March 2026 at the 43rd Annual Miami Breast Cancer Conference.1

The analysis included medical records from 300 patients treated in community oncology settings. The average patient age was 63.5 years; nearly a quarter had impaired performance status, and more than a third had at least one comorbidity or additional health condition.

Seventy-seven percent of patients had hormone receptor–positive disease, 23% had hormone receptor–negative disease, and 24.7% presented with de novo metastatic disease. Most of the patients received T-DXd as monotherapy. Typically, patients with HR-positive BC received T-DXd later in treatment, with most receiving it as third-line therapy or later, and among patients with HR-negative BC, more than half started it before third-line therapy.

Clinical efficacy data showed that overall, the median progression-free survival (PFS) was 7.4 months. For patients with HR-positive disease, the median PFS was 7.7 months, and for those with HR-negative disease, the median PFS was 4.9 months.

The most striking data points were among patients with HR-positive BC without prior chemotherapy for metastatic disease. Median PFS was 10.2 months compared with 7.4 months in those previously treated with chemotherapy. In addition, 74% were alive at 1 year and 71% experienced tumor shrinkage. Patients with brain metastases had a median PFS of 6.3 months, numerically similar to the 7.5 months observed in patients without brain metastases.

Despite being used to treat older patients, those with more comorbidities, and those who had been heavily pretreated, T-DXd demonstrated favorable outcomes, supporting its effectiveness for HER2-low mBC in real-world community oncology settings.