T-DXd Better for Overall Survival than T-DM1 in Metastatic HER2+ Breast Cancer

By Leah Lawrence - Last Updated: December 20, 2022

An updated analysis of survival outcomes from the DESTINY-Breast03 trial has confirmed the superiority of trastuzumab deruxtecan (T-DXd) compared with trastuzumab emtansine (T-DM1) for patients with HER2-positive metastatic breast cancer previously treated with an anti-HER2 therapy.

Sara Hurvitz, MD, a professor of medicine at the David Geffen School of Medicine at the University of California Los Angeles and Jonsson Comprehensive Cancer Center, presented the results at the 2022 San Antonio Breast Cancer Symposium.

Both T-DXd and T-DM1 are antibody drug conjugates approved in the second line for patients with HER2-positive metastatic breast cancer. DESTINY-Breast03, which compared these two drugs in 524 patients, demonstrated that T-DXd yielded significantly longer progression-free survival compared with T-DM1 at an interim analysis.

These new data showed that patients treated with T-DXd had a 36% decreased risk for death compared with those treated with T-DM1 (hazard ratio=0.64; P=.0037). At 1-year, 94.1% of patients assigned to T-DXd were alive compared with 86% of those assigned T-DM1. At 2 years, these rates were 77.4% for T-DXd and 69.9% for T-DM1.

At the symposium, Hurvitz also presented updated progression-free survival data that continued to favor T-DXd. Median progression-free survival was 28.8 months compared with 6.8 months for T-DM1.

Grade 3 or worse treatment-emergent adverse events were reported in 56.4% of the T-DXd arm and 51.7% of the T-DM1 arm. Drug-related interstitial lung disease/pneumonitis occurred in 15.2% of patients assigned T-DXd compared with 3.1% of those assigned T-DM1.

“The results of this analysis demonstrated remarkable overall survival and continued progression-free survival benefit with T-DXd in patients with HER2-positive metastatic breast cancer who progressed on prior therapy, further supporting the use of T-DXd over T-DM1 in the second-line setting,” said Hurvitz. “With this overall survival analysis, we can confirm that the previously demonstrated benefit from T-DXd in PFS improvement transforms into a statistically significant improvement in overall survival, a substantial advantage for our patients.”

Hurvitz SA, Hegg R, Chung W-P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated survival results of the randomized, phase 3 study DESTINY-Breast03. Abstract GS2-02. Presented at 2022 San Antonio Breast Cancer Symposium, San Antonio, Texas.