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This algorithm sequences systemic therapy for advanced triple-negative breast cancer, and the first branch points are PD-L1 status, germline BRCA1/2 status and HER2 expression.
In the first line, patients with PD-L1-positive disease (CPS 10 or higher) receive pembrolizumab plus chemotherapy, supported by KEYNOTE-355, which improved overall survival in this biomarker-selected group, with no benefit shown when CPS was below 10. Patients with germline BRCA1/2 mutations have a targeted option, a PARP inhibitor (olaparib or talazoparib), based on OlympiAD, which improved progression-free survival and response rate versus chemotherapy. PD-L1-negative disease is treated with single-agent chemotherapy, since immunotherapy adds no benefit. In the second line, antibody-drug conjugates are central: trastuzumab deruxtecan for HER2-low disease (IHC 1 to 2+), supported by DESTINY-Breast04, and sacituzumab govitecan, a TROP2-directed agent usable regardless of HER2 status, supported by ASCENT, which improved both progression-free and overall survival over chemotherapy in pretreated metastatic TNBC.
Background reading: Breast Cancer (Part 2): DCIS, Early-Stage and Metastatic Treatment board review notes.
Starting point: Advanced TNBC by PD-L1, gBRCA, HER2 status. Full background: Breast Cancer (Part 2): DCIS, Early-Stage and Metastatic Treatment notes.