Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer
- PMID: 35665782
- PMCID: PMC10561652
- DOI: 10.1056/NEJMoa2203690
Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer
Abstract
Background: Among breast cancers without human epidermal growth factor receptor 2 (HER2) amplification, overexpression, or both, a large proportion express low levels of HER2 that may be targetable. Currently available HER2-directed therapies have been ineffective in patients with these "HER2-low" cancers.
Methods: We conducted a phase 3 trial involving patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy. (Low expression of HER2 was defined as a score of 1+ on immunohistochemical [IHC] analysis or as an IHC score of 2+ and negative results on in situ hybridization.) Patients were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival in the hormone receptor-positive cohort. The key secondary end points were progression-free survival among all patients and overall survival in the hormone receptor-positive cohort and among all patients.
Results: Of 557 patients who underwent randomization, 494 (88.7%) had hormone receptor-positive disease and 63 (11.3%) had hormone receptor-negative disease. In the hormone receptor-positive cohort, the median progression-free survival was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician's choice group (hazard ratio for disease progression or death, 0.51; P<0.001), and overall survival was 23.9 months and 17.5 months, respectively (hazard ratio for death, 0.64; P = 0.003). Among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician's choice group (hazard ratio for disease progression or death, 0.50; P<0.001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = 0.001). Adverse events of grade 3 or higher occurred in 52.6% of the patients who received trastuzumab deruxtecan and 67.4% of those who received the physician's choice of chemotherapy. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 12.1% of the patients who received trastuzumab deruxtecan; 0.8% had grade 5 events.
Conclusions: In this trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician's choice of chemotherapy. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast04 ClinicalTrials.gov number, NCT03734029.).
Copyright © 2022 Massachusetts Medical Society.
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Comment in
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T-DXd active in HER2-low disease.Nat Rev Clin Oncol. 2022 Aug;19(8):493. doi: 10.1038/s41571-022-00663-9. Nat Rev Clin Oncol. 2022. PMID: 35778612 No abstract available.
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DESTINY-Changing Results for Advanced Breast Cancer.N Engl J Med. 2022 Jul 7;387(1):75-76. doi: 10.1056/NEJMe2206661. N Engl J Med. 2022. PMID: 35793210 No abstract available.
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Trastuzumab Deruxtecan in HER2-Low Breast Cancer.N Engl J Med. 2022 Sep 22;387(12):1143-1144. doi: 10.1056/NEJMc2210368. N Engl J Med. 2022. PMID: 36130004 No abstract available.
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Trastuzumab Deruxtecan in HER2-Low Breast Cancer.N Engl J Med. 2022 Sep 22;387(12):1144. doi: 10.1056/NEJMc2210368. N Engl J Med. 2022. PMID: 36130005 No abstract available.
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Clinical Potential of HER2 PET as a Predictive Biomarker to Guide the Use of Trastuzumab Deruxtecan in Breast Cancer Patients.J Nucl Med. 2023 Jul;64(7):1164-1165. doi: 10.2967/jnumed.123.265434. Epub 2023 May 25. J Nucl Med. 2023. PMID: 37230529 No abstract available.
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