A new phase III study has demonstrated the efficacy of trastuzumab deruxtecan (Enhertu) in patients with HER2-positive metastatic breast cancer whose cancers were resistant to previous treatment with trastuzumab emtansine. Both trastuzumab deruxtecan and trastuzumab emtansine are antibody-drug conjugates, a relatively new type of drug that delivers chemotherapy directly to the cancer cell, minimizing damage to normal tissues. The study was published in The Lancet on April 19, 2023.
"The results from this trial confirm the high degree of effectiveness of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer that have already developed resistance to other treatments,” said Ian Krop, MD, PhD, senior author of the paper and chief clinical research officer at Yale Cancer Center. "Importantly, this study is also the first to definitively show that one antibody-drug conjugate can be effective even after another antibody-drug conjugate has stopped working. This is encouraging because it means we can use these new and promising drugs one after another to improve the lives of patients with this disease,” Dr. Krop added.
The study was based on results from the DESTINY-Breast02 trial – conducted at 227 sites around the world – that randomly assigned 608 eligible patients aged 18 years or older to either receive trastuzumab deruxtecan or a physician's choice of treatment. The study found that patients who received trastuzumab deruxtecan had significantly longer survival compared to those who received physician's choice of treatment. Median overall survival was 12.7 months longer in the trastuzumab deruxtecan group compared to those in the treatment of the physician's choice group.
The most common adverse events observed in patients in the trastuzumab deruxtecan group were nausea and vomiting, which were typically mild. Drug-related interstitial lung disease occurred in 10% of patients receiving trastuzumab deruxtecan, including 0.5% of patients who died from this adverse event. After analyzing the data, researchers found that trastuzumab deruxtecan had a favorable benefit-risk profile.
The study was funded by Daiichi Sankyo and AstraZeneca.