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Given as the first chemotherapy-type treatment after hormone therapy stopped working, trastuzumab deruxtecan delayed progression by about five months compared with standard chemotherapy, including in tumours with barely detectable HER2.
Open-label phase 3 trial of 866 patients with hormone-receptor-positive metastatic breast cancer that was HER2-low (IHC 1+ or 2+/ISH-negative) or HER2-ultralow (IHC 0 with faint membrane staining), who had progressed on endocrine therapy but had not received chemotherapy for metastatic disease. Patients were randomised to trastuzumab deruxtecan or physician's choice chemotherapy (capecitabine, paclitaxel or nab-paclitaxel). Primary endpoint was PFS in the HER2-low group.
Median PFS was 13.2 vs 8.1 months (HR 0.62) in HER2-low patients, with a similar effect in the ultralow subgroup. It moved T-DXd one line earlier and pushed the HER2 threshold down to almost any detectable staining.
Patients with hormone-receptor-positive metastatic breast cancer that has stopped responding to endocrine therapy can be offered trastuzumab deruxtecan as their first chemotherapy-type treatment if the tumour shows any HER2 staining, rather than waiting until after conventional chemotherapy. Whether to use it before or after chemotherapy is now a choice, since overall survival was not shown to differ and the drug carries a risk of lung inflammation.
Shares Joohyuk Sohn, Seock-Ah Im, Interstitial lung disease (ILD) / pneumonitis, HER2-low and HER2-ultralow.
Shares Carlos Barrios, Seock-Ah Im, Daiichi Sankyo, Progression-free survival (PFS).
Shares HER2-low and HER2-ultralow metastatic breast cancer, HER2-low and HER2-ultralow, Daiichi Sankyo, Immunohistochemistry (IHC).
Shares Seock-Ah Im, Giuseppe Curigliano, Interstitial lung disease (ILD) / pneumonitis, Daiichi Sankyo.
Shares Calibrated reference slides so every lab scores HER2-low the same way, HER2-low and HER2-ultralow metastatic breast cancer, HER2-low and HER2-ultralow, Daiichi Sankyo.
Shares Calibrated reference slides so every lab scores HER2-low the same way, DESTINY-Breast06, HER2-low and HER2-ultralow, Immunohistochemistry (IHC).
Shares HER2-low and HER2-ultralow metastatic breast cancer, Daiichi Sankyo, Trastuzumab deruxtecan, AstraZeneca.
Shares DESTINY-Breast06, HER2-low and HER2-ultralow, Trastuzumab deruxtecan, Histopathology & immunohistochemistry.