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Breast cancers with only a little HER2 on their surface, long called HER2-negative, responded to trastuzumab deruxtecan and patients lived about six months longer than on chemotherapy. It created the HER2-low category.
Open-label phase 3 trial of 557 patients with HER2-low (IHC 1+ or IHC 2+/ISH-negative) metastatic breast cancer after one or two lines of chemotherapy, randomised 2:1 to trastuzumab deruxtecan or physician's choice chemotherapy. About 89% were hormone-receptor positive. Primary endpoint was PFS in the HR-positive cohort.
Median PFS was 10.1 vs 5.4 months (HR 0.51) in the HR-positive cohort and overall survival 23.9 vs 17.5 months (HR 0.64); results in the whole population were similar. Roughly half of all breast cancers are HER2-low, so the trial redefined HER2 testing and opened ADC therapy to a very large population.
Patients whose breast cancer was previously called HER2-negative may now be eligible for an effective HER2-directed drug if their tumour has even low-level HER2 staining, so pathology reports must now distinguish HER2-low (1+ or 2+/ISH-negative) from HER2-zero. This applies to metastatic disease after at least one line of chemotherapy; it does not mean these patients benefit from trastuzumab or other older HER2 drugs.
Shares Yeon Hee Park, Sung-Bae Kim, Seock-Ah Im, Binghe Xu.
Shares Joohyuk Sohn, Seock-Ah Im, Interstitial lung disease (ILD) / pneumonitis, HER2-low and HER2-ultralow.
Shares Reflex re-scoring of HER2 0 versus 1+ with digital assistance so every eligible triple-negative patient reaches trastuzumab deruxtecan, Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer, HER2-low (IHC 1+ or IHC 2+/ISH-negative), HER2-low and HER2-ultralow.
Shares Seock-Ah Im, Binghe Xu, Payload-class switching as the rule for ADC sequencing, Daiichi Sankyo.
Shares Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer, HER2-low (IHC 1+ or IHC 2+/ISH-negative), DESTINY-Breast04, HER2-low and HER2-ultralow.
Shares Reflex re-scoring of HER2 0 versus 1+ with digital assistance so every eligible triple-negative patient reaches trastuzumab deruxtecan, Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer, HER2-low (IHC 1+ or IHC 2+/ISH-negative), DESTINY-Breast04.
Shares Hope S. Rugo, A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer, Progression-free survival (PFS), Overall survival (OS).
Shares HER2-low (IHC 1+ or IHC 2+/ISH-negative), HER2-low and HER2-ultralow, Immunohistochemistry (IHC), Trastuzumab deruxtecan.