Initial treatment of metastatic triple-negative breast cancer

BRCA: breast cancer susceptibility gene; PD-L1: programmed cell death-ligand 1; PARP: polyadenosine diphosphate-ribose polymerase; ER: estrogen receptor; PR: progesterone receptor; HER2: human epidermal growth factor receptor 2; IHC: immunohistochemistry; FISH: fluorescence in situ hybridization; FDA: US Food and Drug Administration; OS: overall survival; TNBC: triple-negative breast cancer; CPS: combined positive score.
* Combination chemotherapy may be appropriate for those with extensive or rapidly progressive visceral disease, in whom the higher chance of response is thought to outweigh the higher risks of toxicity due to concerns about impending organ dysfunction. However, it should be recognized that no prospective data have shown combination chemotherapy improves overall survival compared with single-agent sequential cytotoxic chemotherapy.
¶ We often start with a PARP inhibitor rather than chemotherapy given the potential for disease control with fewer toxicities compared with chemotherapy, and proceed with atezolizumab and nabpaclitaxel upon progression. However, some experts reasonably offer atezolizumab and nabpaclitaxel ahead of a PARP inhibitor for those with PD-L1-positive, BRCA-positive, triple-negative breast cancer.
Δ Pembrolizumab is approved by the FDA in combination with chemotherapy for patients with metastatic TNBC whose tumors express PD-L1 with a CPS ≥10 (the percentage of total cells [tumor cells, lymphocytes, macrophages] that stain for PD-L1).^[1] Although atezolizumab previously was granted accelerated approval, regulatory approval has been withdrawn given subsequent trial results.
◊ For BRCA-associated breast cancers, taxanes and platinum agents appear to be equally effective as first-line agents. By contrast, for non-BRCA-associated breast cancers, platinum-based chemotherapy has inferior response rates when compared with taxane-based treatment in the first-line setting.