Trial results for Trastuzumab Deruxtecan (T-DXd) in HER2-low, hormone receptor-positive, metastatic breast cancer were posted on ClinicalTrials.gov on 2025-04-02. The study showed a median progression-free survival (PFS) of 13.2 months for T-DXd compared to 8.1 months for investigator's choice chemotherapy.
Background
The study evaluated the efficacy, safety, and tolerability of trastuzumab deruxtecan against investigator's choice chemotherapy in human epidermal growth factor receptor (HER)2-low, hormone receptor (HR) positive breast cancer patients whose disease had progressed on endocrine therapy in the metastatic setting.
Trial design
The study (NCT04494425) was a Phase 3 trial that enrolled 866 participants with advanced or metastatic breast cancer. It compared trastuzumab deruxtecan (T-DXd) with investigator's choice chemotherapy, which included capecitabine, paclitaxel, or nab-paclitaxel. The trial's objective was to evaluate trastuzumab deruxtecan in HER2-low, HR-positive breast cancer patients whose disease had progressed on endocrine therapy in the metastatic setting.
Key results
The trial results demonstrated improved progression-free survival (PFS) for trastuzumab deruxtecan compared to chemotherapy. In the hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low population, the median PFS for the T-DXd group was 13.2 months, while for the chemotherapy group it was 8.1 months.
For overall survival (OS) in the same HR+, HER2-low population, the median OS was 28.9 months for T-DXd and 27.1 months for chemotherapy. In the intent-to-treat population, the median OS was 28.9 months for T-DXd and 27.4 months for chemotherapy.
A statistical analysis using the Log Rank method reported a Hazard Ratio (HR) of 0.62 (95.0% CI: 0.52 to 0.75) with a p-value of 0.0001, indicating a statistically significant reduction in the risk of progression or death with trastuzumab deruxtecan.
What this means
The results suggest that trastuzumab deruxtecan offers a clinically meaningful improvement in progression-free survival for patients with HER2-low, HR-positive, metastatic breast cancer whose disease has progressed on endocrine therapy. The observed increase in median PFS and the favorable hazard ratio indicate that trastuzumab deruxtecan could be an important treatment option for this patient population.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04494425, titled "Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Canc", were posted on 2025-04-02 on clinicaltrials.gov.