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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Tuesday, January 28, 2025
The antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) has been approved by the U.S. Food and Drug Administration (FDA) for treatment of adults with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH–) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-approved test, that has progressed on one or more endocrine therapies in the metastatic setting, according to a recent announcement by Daiichi Sankyo and AstraZeneca.
The approval was based on results from the phase III DESTINY-Breast06 trial, which were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine. DESTINY-Breast06 enrolled 866 patients (713 with HER2-low disease and 153 with HER2-ultralow disease) in Asia, Europe, North America, Oceania, and South America.
In the trial, use of T-DXd yielded a 36% reduction in the risk of disease progression or death vs chemotherapy (hazard ratio [HR] = 0.64; 95% confidence interval [CI] = 0.54–0.76; P < .0001) in the overall trial population of patients with chemotherapy-naive HER2-low or HER2-ultralow metastatic breast cancer. A median progression-free survival of 13.2 months was seen in patients randomly assigned to receive T-DXd compared with 8.1 months in those randomly assigned to chemotherapy. The confirmed objective response rate in the overall trial population was 62.6% with T-DXd vs 34.4% with chemotherapy.
The confirmed objective response rate in the overall trial population was 62.6% (95% CI = 57.6%–67.4%) with T-DXd vs 34.4% (95% CI = 29.7%–39.4%) with chemotherapy, as assessed by blinded independent central review. There were 10 complete responses (2.5%) and 236 partial responses (60.1%) reported with T-DXd vs 0 complete responses and 134 partial responses (34.4%) with chemotherapy. The median duration of response was 14.3 months in the T-DXd arm (95% CI = 12.5–15.9 months) vs 8.6 months in the chemotherapy arm (95% CI = 6.9–11.5 months), as assessed by blinded independent central review.
The safety profile of T-DXd in DESTINY-Breast06 was consistent with previous clinical trials of this agent in breast cancer, with no new safety concerns identified.
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