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William J. Gradishar, MD, FACP, FASCO


T-DXd Versus T-DM1 in Metastatic Breast Cancer: Subgroup Analyses From DESTINY-Breast03

By: Lauren Harrison, MS
Posted: Friday, January 14, 2022

Trastuzumab deruxtecan (T-DXd) for treatment of patients with HER2-positive metastatic breast cancer led to improvement in survival rates when compared with the standard of care (trastuzumab emtansine [T-DM1]), according to the phase III DESTINY-Breast03 trial. This survival benefit was seen across subgroups of patients who were previously treated with trastuzumab and taxane, including those with brain metastases. Sara Hurvitz, MD, of the University of California, Los Angeles, presented these findings on behalf of her colleagues at the 2021 San Antonio Breast Cancer Symposium (Abstract GS3-01). 

This study enrolled 524 patients with HER2-positive metastatic breast cancer, including patients with stable brain metastases. Patients were randomly assigned 1:1 to receive either 5.4 mg/kg of T-DXd or 3.6 mg/kg of T-DM1 every 3 weeks. Lesions were measured using the modified Response Evaluation Criteria in Solid Tumors version 1.1.

The median progression-free survival for the group receiving T-DXd was not yet reached, and it was 6.8 months for the T-DM1 group (hazard ratio = 0.28, P < .001). For patients with brain metastases at baseline, the median progression-free survival was 15 months with T-DXd and 3 months with T-DM1 (hazard ratio = 0.25). The confirmed overall response rate was 79.7% with T-DXd and 34.2% with T-DM1. In the subgroup of patients with brain metastases, the overall response rate was 67.4% in the experimental group and 20.5% in the control group. At the time of data cutoff, 32.2% of patients treated with T-DXd had progressive disease, compared with 58.9% of patients receiving standard therapy.

The safety profile for T-DXd was reported to be manageable and comparable to previously known data. Adjudicated drug-related interstitial lung disease or pneumonitis was reported in 10.5% of patients in the experimental group and 1.9% of patients in the control group. There were no grade 4 or 5 events noted.

Disclosure: For a full list of authors’ disclosures, visit

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