Breast Cancer Coverage from Every Angle

ESMO 2021: DESTINY-Breast03 Trial of T-DXd Versus T-DM1 in HER2-Positive Breast Cancer

By: Vanessa A. Carter, BS
Posted: Thursday, September 23, 2021

Javier Cortés, MD, PhD, of the International Breast Cancer Center, Barcelona, and colleagues compared the safety and efficacy of fam-trastuzumab deruxtecan-nxki (T-DXd) versus trastuzumab emtansine (T-DM1)—HER2-targeting antibody–drug conjugates—in patients with HER2-positive breast cancer. Presented during the European Society for Medical Oncology (ESMO) Congress 2021 (Abstract LBA1), the phase III DESTINY-Breast03 study reported that T-DXd demonstrated a clinically meaningful and statistically significant improvement in progression-free survival and compared with T-DM1.

“In the past 8 years, we have not seen any other therapy try to beat [T-DM1] in a head-to-head trial,” stated study coauthor Sara Hurvitz, MD, of UCLA Jonsson Comprehensive Cancer Center, in an institutional press release. “Seeing a new therapy demonstrate such a substantial improvement in progression- free survival compared to T-DM1 is really exciting for our patients.”

This study enrolled 524 patients with HER2-positive, metastatic breast cancer previously treated with trastuzumab and taxane. Participants were randomly assigned to receive T-DXd (n = 261) or T-DM1 (n = 263).

Although the median progression-free survival was not reached for patients given T-DXd, patients in the T-DM1 arm had a median progression-free survival of 6.8 months (hazard ratio [HR] = 0.28); median progression-free survival by investigator assessment was 25.1 versus 7.2 months. The 12-month overall survival rates were estimated to be 94.1% for T-DXd and 85.9% for T-DM1 (HR = 0.55), but they did not cross the prespecified boundary for significance. The objective response rate was 79.1% in the T-DXd arm, compared with 34.2% in the T-DM1 arm. Notably, 16% of participants experienced complete remission.

The median duration of treatment for T-DXd was 14.3 months, and for T-DM1, 6.9 months. Treatment-emergent adverse events of any grade affected almost all patients in both the T-DXd (99.6%) and T-DM1 (95.4%) groups. Although no drug-related deaths were observed, adverse events of grade 3 or higher and serious adverse events occurred at a similar frequency in each arm.

Disclosure: For full disclosures of the study authors, visit

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