Trastuzumab Deruxtecan Improves Progression-Free Survival for Certain Patients With Breast Cancer

Trastuzumab deruxtecan (Enhertu, AstraZeneca and Daiichi Sankyo) demonstrated superiority over trastuzumab emtansine (T-DM1) in the results from the head-to-head DESTINY-Breast03 phase 3 trial, according to a press release from AstraZeneca. The Independent Data Monitoring Committee concluded that DESTINY-Breast03 met the primary endpoint of progression-free survival and showed a highly statistically significant and clinically meaningful improvement for patients with human epidermal growth factor receptor 2 (HER2)-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

“There is a continued need for new options and better outcomes for patients with HER2-positive metastatic breast cancer who often experience disease progression after initial treatment with available standards of care,” said Susan Galbraith, PhD, executive vice president of oncology R&D at AstraZeneca, in a press release. “These transformative progression-free survival results demonstrate the superiority of Enhertu compared to T-DM1, and the encouraging safety data may open future opportunities to bring this benefit to patients in earlier treatment settings.”

According to the investigators, trastuzumab deruxtecan also demonstrated a strong trend toward improved overall survival (OS) compared to T-DM1, although the data for OS are still immature. Further, there were no new safety concerns identified and no grade 4 or 5 treatment-related interstitial lung disease events, indicating that the safety profile for trastuzumab deruxtecan was consistent with previous clinical trials, according to the researchers.

“DESTINY-Breast03 is the first global phase 3 head-to-head trial of Enhertu against an active control and supports the potential of this medicine to become the new standard of care for patients with HER2-positive metastatic breast cancer following initial treatment with trastuzumab and a taxane,” said Ken Takeshita, MD, global head of research and development at Daiichi Sankyo, in the release. “We believe this highly sophisticated and specifically engineered ADC is fulfilling its promise to reshape the treatment of HER2-positive metastatic breast cancer, with the goal to move into earlier lines of treatment for HER2-positive breast cancer and many other HER2-expressing tumor types across our broad clinical trial program.”

Trastuzumab deruxtecan is being evaluated for efficacy and safety across multiple HER2-targetable cancers in a comprehensive clinical development program. These include breast, gastric, lung, and colorectal cancers.

REFERENCE

Enhertu significantly improved progression-free survival in DESTINY-Breast03 head-to-head trial vs. trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer [news release]. AstraZeneca; August 9, 2021. Accessed August 9, 2021. https://www.astrazeneca.com/media-centre/press-releases/2021/enhertu-head-to-head-trial-meets-primary-endpoint.html