Enhertu (trastuzumab deruxtecan), developed by AstraZeneca and Daiichi Sankyo has been approved by The FDA to treat adult patients with unresectable or metastatic hormone receptor-positive, HER2-low or HER2-ultralow breast cancer.
The patients have experienced disease progression after receiving one or more endocrine therapies in the metastatic stage, as confirmed by an FDA-approved diagnostic test.
In this study titled “Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer” published on The New England Journal of Medicine, Outcomes in patients with hormone receptor–positive metastatic breast cancer tend to decline after receiving one or more lines of endocrine-based therapy. Trastuzumab deruxtecan has demonstrated effectiveness in patients with metastatic breast cancer who exhibit low expression of human epidermal growth factor receptor 2 (HER2) following prior chemotherapy treatments.
Authors: Aditya Bardia, Xichun Hu, Rebecca Dent, Kan Yonemori, Carlos H. Barrios, Joyce A. O’Shaughnessy, Hans Wildiers, Jean-Yves Pierga, Qingyuan Zhang, Cristina Saura, Laura Biganzoli, Joohyuk Sohn, Seock-Ah Im, Christelle Lévy, William Jacot, Natasha Begbie, Jun Ke, Gargi Patel, Giuseppe Curigliano
In the study involving 866 patients, 713 had HER2-low disease, and 153 had HER2-ultralow disease. For those with HER2-low disease, the median progression-free survival was 13.2 months in the trastuzumab deruxtecan group compared to 8.1 months in the chemotherapy group. The hazard ratio for disease progression or death was 0.62, indicating a significant benefit for trastuzumab deruxtecan. These results were consistent in the HER2-ultralow group as well. However, overall survival data were not yet mature.
Grade 3 or higher adverse events occurred in 52.8% of the patients treated with trastuzumab deruxtecan, while 44.4% of those in the chemotherapy group experienced similar adverse events. Interstitial lung disease or pneumonitis was observed in 11.3% of patients receiving trastuzumab deruxtecan, with three events being grade 5 in severity. In contrast, only 0.2% of patients in the chemotherapy group experienced this side effect.
Aditya Bardia, Director of translational research integration at UCLA Health Jonsson Comprehensive Cancer Center, added:
“Endocrine therapy is typically used in the initial treatment of HR-positive metastatic breast cancer and following progression, subsequent chemotherapy is associated with poor outcomes. With a median progression-free survival exceeding one year and a response rate of more than 60 per cent, trastuzumab deruxtecan offers a potential new standard of care for patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer following endocrine therapy.”
About Trastuzumab deruxtecan
Enhertu is a HER2-targeted antibody-drug conjugate (ADC) developed using Daiichi Sankyo’s proprietary DXd ADC Technology. As the leading ADC in Daiichi Sankyo’s oncology portfolio and the most advanced program in AstraZeneca’s ADC platform, Enhertu combines a HER2-specific monoclonal antibody with multiple topoisomerase I inhibitor payloads (an exatecan derivative, DXd), connected by tetrapeptide-based cleavable linkers.
Approved in over 75 countries, Enhertu (5.4mg/kg) is indicated for adult patients with unresectable or metastatic HER2-positive breast cancer (IHC 3+ or ISH+), who have previously received one or more anti-HER2 treatments either in the metastatic, neoadjuvant, or adjuvant settings and have experienced disease recurrence during or within six months of completing therapy. This approval is supported by data from the DESTINY-Breast03 trial. Additionally, Enhertu is also approved for the treatment of adult patients with unresectable or metastatic HER2-low breast cancer (IHC 1+ or IHC 2+/ISH-), who have previously received systemic therapy in the metastatic setting or experienced disease recurrence within six months after adjuvant chemotherapy, based on the results from the DESTINY-Breast04 trial.