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Activity of olaparib in patients with BRCA-mutated early breast cancer
27/06/2022DESTINY-Breast04 study presented at ASCO shows significant and practice changing clinical benefits in HER2-low patients treated with trastuzumab deruxtecan
Results of the DESTINY-Breast04 study, featured in ASCO 2022, could change clinical practice in patients with HER2-low metastatic breast cancer: treatment with the antibody-drug conjugate trastuzumab deruxtecan (T-Dxd) significantly improved progression-free survival and overall survival when compared to the physician’s choice of chemotherapy. The result, simultaneously published on The New England Journal of Medicine, were also acclaimed with a standing ovation following the oral presentation during the meeting in Chicago.
The drug T-Dxd is comprised of a HER2-targeted monoclonal antibody that delivers high concentrations of chemotherapy directly to cancer cells that have HER2 on their surface. In the phase III trial DESTINY-Breast04, 557 patients were randomized to receive T-Dxd or physician’s choice of chemotherapy; all had previously received one or two previous lines of chemotherapy, 88.7% had hormone receptor–positive disease and 11.3% had hormone receptor–negative disease. Results show that T-Dxd is significantly better than chemotherapy: in the hormone receptor–positive cohort T-Dxd resulted in a median progression-free survival of 10.1 months vs 5.4 in the physician’s choice group and overall survival was 23.9 months and 17.5 months, respectively; among all patients, the median progression-free survival was 9.9 months in the T-Dxd group and 5.1 months in the physician’s choice group, and overall survival was 23.4 months and 16.8 months, respectively. These striking results were correlated with a good safety profile: adverse events of grade 3 or higher occurred in 52.6% of the patients who received T-Dxd and 67.4% of those who received the physician’s choice of chemotherapy.
T-Dxd received accelerated approval by the Food and Drug Administration in 2019 for patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. These new data show that T-Dxd can lead to a significantly longer progression-free and overall survival than the physician’s choice of chemotherapy among patients with HER2-low metastatic breast cancer, regardless of hormone-receptor status. These results have the potential to improve the treatment outcome for more than half of patients historically categorized as having HER2-negative breast cancer.
