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Three antibody-drug conjugates now used in triple-negative breast cancer carry the same kind of chemotherapy warhead, a topoisomerase inhibitor. Nobody has randomised which to give first or whether the second works after the first; small series suggest it often does not. With two now approved first line, the question decides what a patient gets for the rest of her life.
Sacituzumab govitecan (SN-38) and datopotamab deruxtecan and trastuzumab deruxtecan (deruxtecan) all deliver topoisomerase I inhibitor payloads; ASCENT-03, ASCENT-04 and TROPION-Breast02 moved the TROP2 conjugates to first line and DESTINY-Breast04 covers the 36.6 percent of triple-negative tumours that are HER2-low. Retrospective series of conjugate after conjugate report short progression-free survival on the second agent, consistent with payload resistance (SLFN11 loss, TOP1 mutation) rather than antigen loss, and the corpus term adc-after-adc-caution records the position. No randomised trial compares TROP2 conjugate then trastuzumab deruxtecan with the reverse, or tests chemotherapy interposition, and the ASCO 2022 biomarker guideline finds no test to guide the choice.
The first-line overall survival result that made an antibody-drug conjugate the standard for PD-L1-negative or immunotherapy-ineligible metastatic triple-negative disease, and the reason the sequencing question (which TROP2 drug first, what after it) is now urgent.
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.
Confirms that the TROP2 antibody-drug conjugates are given without a TROP2 test and that PD-L1 remains the one selection assay in metastatic triple-negative disease, which is why assay harmonisation matters.
Sacituzumab govitecan is a standard second-line or later treatment for metastatic triple-negative breast cancer, roughly doubling survival compared with the chemotherapies it was tested against. Patients should expect neutropenia and diarrhoea, which are manageable with growth factor support and loperamide. Trials are now testing it earlier, in first-line combinations with pembrolizumab and after surgery for residual disease.
Shares DESTINY-Breast04, DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group, HER2-low and HER2-ultralow metastatic breast cancer, HER2-low and HER2-ultralow and the tag tnbc-evidence.
Shares DESTINY-Breast04, DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group, HER2-low and HER2-ultralow metastatic breast cancer, HER2-low and HER2-ultralow and the tag tnbc-evidence.
Shares Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial, Datopotamab deruxtecan, Sacituzumab govitecan, Trastuzumab deruxtecan and the tag tnbc-evidence.
Shares ASCENT-03, TROPION-Breast02, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Datopotamab deruxtecan, Sacituzumab govitecan, Trial design, endpoints and cost, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem and the tag tnbc-evidence.
Shares Progression-free survival (PFS), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, AstraZeneca, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, HER2, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.