Metastatic Triple-Negative Breast Cancer

Sequencing for triple-negative metastatic breast cancer: PD-L1 CPS decides first-line chemoimmunotherapy, germline BRCA status selects a PARP inhibitor otherwise, and sacituzumab govitecan anchors the second line.

PD-L1 combined positive score (CPS)?

• PD-L1 CPS ≥ 10 → Pembrolizumab + chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin)
• PD-L1 CPS < 10 → Germline BRCA1/2 mutation?

1L: Pembrolizumab + chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin)

PD-L1 CPS ≥10: add pembrolizumab to first-line chemotherapy. Monitor for immune-related adverse events.

Evidence: KEYNOTE-355

• Progression → Sacituzumab govitecan

Germline BRCA1/2 mutation?

• Germline BRCA1/2 mutation → PARP inhibitor (olaparib or talazoparib)
• BRCA wild-type → Single-agent chemotherapy (taxane or gemcitabine/carboplatin)

1L: PARP inhibitor (olaparib or talazoparib)

Germline BRCA1/2-mutated PD-L1-negative disease: a PARP inhibitor is preferred over single-agent chemotherapy. Monitor CBC for cytopenias.

• Progression → Sacituzumab govitecan

1L: Single-agent chemotherapy (taxane or gemcitabine/carboplatin)

PD-L1-negative, BRCA wild-type: sequential single-agent chemotherapy is standard.

• Progression → Sacituzumab govitecan

2L: Sacituzumab govitecan

Trop-2-directed antibody-drug conjugate; improves survival after ≥1 prior chemotherapy. Monitor neutropenia and diarrhea (UGT1A1 status informs risk).

Evidence: ASCENT

• Progression → Further single-agent chemotherapy (eribulin, capecitabine)

3L+: Further single-agent chemotherapy (eribulin, capecitabine)

Sequential single agents by tolerability; strongly consider a clinical trial.