Trastuzumab deruxtecan demonstrated clinically meaningful and statistically significant improvements in overall and progression-free survival, the company says.
AstraZeneca announced positive results from the DESTINY-Breast04 phase 3 trial of trastuzumab deruxtecan (Enhertu, AstraZeneca, Daiichi Sankyo) in individuals with HER2-low unresectable and/or metastatic breast cancer, regardless of hormone receptor (HR) status versus the physician’s choice of chemotherapy.
Trastuzumab deruxtecan, a HER2-directed antibody drug conjugate, showed clinically meaningful and statistically significant improvements in both overall survival (OS) and progression-free survival (PFS) for this population.
“These results for Enhertu are a huge step forward and could potentially expand our ability to target the full spectrum of HER2 expression, validating the need to change the way we categorize and treat breast cancer,” Susan Galbraith, executive vice president for oncology research and development at AstraZeneca said in a statement.
All individuals in the trial received a HER2 test and had their results confirmed. HER2-low status was defined as an immunohistochemistry (IHC) score of 1+ or IHC 2+ with a negative in-situ hybridization (ISH) score.
Additionally, up to 55% individuals with breast cancer tumors with a HER2 IHC score of 1+ or 2+, with a negative ISH test are not eligible for HER2-targeted therapy. HER2 testing is an established way to determine treatment strategies in metastatic breast cancer.
Furthermore, targeting the lower range of HER2 expression could potentially offer another approach to delay disease progression and extend survival. Chemotherapy remains the only treatment option for individuals with HR-positive tumors following progression on endocrine hormone therapy and those who are HR-negative.
DESTINY-Breast04 is a global, open-label, randomized phase 3 trial comparing the efficacy and safety of trastuzumab deruxtecan with chemotherapy.
The trial met its primary endpoint, demonstrating superior PFS in previously treated individuals with HR-positive HER2-low metastatic breast cancer when treated with trastuzumab deruxtecan compared with the standard-of-care chemotherapy.
Additionally, the study met its key secondary endpoint of PFS in individuals with HER2-low metastatic breast cancer, regardless of HR-status. Furthermore, it met key secondary endpoints of OS in individuals with HR-positive disease and in individuals, regardless of HR status at interim analysis.
The safety profile of trastuzumab deruxtecan was consistent with previous clinical trials, and there were no new safety concerns identified. The overall interstitial lung disease (ILD) rates were consistent with those observed in late-line HER2-positive breast cancer trials of trastuzumab deruxtecan with lower rates of Grade 5 ILD observed as determined by an independent adjudication committee.
The data will be presented at a forthcoming medical meeting and will also be shared with global health authorities.
Trastuzumab deruxtecan has been approved in more than 40 countries for the treatment of adults with unresectable or metastatic HER2-positive breast cancer who has received 2 or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast-1 trial.
In addition, trastuzumab deruxtecan is further being assessed in a comprehensive clinical development program that is aimed at evaluating efficacy and safety across multiple HER2-targetable cancer, which includes breast, colorectal, gastric, and lung cancer.
Enhertu significantly improved both progression-free and overall survival in DESTINY-Breast04 trial in patients with HER2-low metastatic breast cancer. AstraZeneca. News release. February 21, 2022. Accessed February 22, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/enhertu-improves-pfs-and-os-in-her2-low-bc.html