What is the treatment for metastatic triple negative breast cancer?

Treatment for Metastatic Triple-Negative Breast Cancer

For patients with metastatic triple-negative breast cancer (TNBC), the optimal treatment approach depends on PD-L1 status, BRCA mutation status, and prior treatment history, with immune checkpoint inhibitors plus chemotherapy being the preferred first-line option for PD-L1-positive disease, and sacituzumab govitecan recommended after two prior therapies for metastatic disease. 1

First-Line Treatment Options

PD-L1 Positive Disease

• Patients with PD-L1-positive metastatic TNBC should receive immune checkpoint inhibitor plus chemotherapy as first-line therapy (atezolizumab plus nab-paclitaxel or pembrolizumab plus chemotherapy) 1
• This combination has demonstrated improved progression-free survival compared to chemotherapy alone 1

PD-L1 Negative Disease

• Single-agent chemotherapy is preferred for first-line treatment in PD-L1-negative disease 1
• Combination chemotherapy may be considered for patients with symptomatic or immediately life-threatening disease 1
• Either platinum-based or non-platinum-based regimens are appropriate, with selection based on individual risk-benefit assessment 1

Recommended First-Line Chemotherapy Options

• Taxanes (paclitaxel or docetaxel) are preferred if not previously used in the adjuvant setting 1
• Anthracyclines (doxorubicin, epirubicin) if not previously used 1
• Platinum agents (carboplatin, cisplatin) with or without taxanes 1
• Albumin-bound paclitaxel plus carboplatin has shown superior PFS (8.3 months) compared to other combinations in the tnAcity trial 1

Second-Line and Beyond Treatment

For Patients with BRCA1/2 Mutations

• PARP inhibitors (olaparib or talazoparib) are recommended rather than chemotherapy for patients with germline BRCA1/2 mutations who have received prior chemotherapy 1
• These agents can be used in first through third-line settings 1

For Patients After Two Prior Therapies

• Sacituzumab govitecan is strongly recommended for patients who have received at least two prior therapies for metastatic disease 1
• The ASCENT trial demonstrated significant improvement in both PFS (5.6 vs 1.7 months) and OS (12.1 vs 6.7 months) compared to standard chemotherapy 1

Other Chemotherapy Options After Progression

• If previously treated with taxanes, consider anthracyclines and vice versa 1, 2
• Additional options include:
  • Capecitabine/docetaxel (if not previously used) 1
  • Gemcitabine/paclitaxel 1, 3
  • Eribulin (particularly in the triple-negative subset) 1
  • Single-agent capecitabine, gemcitabine, vinorelbine 1, 2

Treatment Considerations and Caveats

• Sequential single-agent chemotherapy is generally preferred over combination regimens to minimize toxicity, except in cases of visceral crisis or rapidly progressing disease 1
• Combination regimens may offer higher response rates but often with increased toxicity 1
• Platinum agents have shown particular efficacy in TNBC, with potential small survival benefits, but with increased toxicity including nausea, vomiting, and anemia 1, 4
• Treatment should be maintained until disease progression or unacceptable toxicity 2
• Bevacizumab combined with chemotherapy (particularly paclitaxel) has shown improved progression-free survival but not overall survival in some studies 1

Monitoring and Dose Adjustments

• Monitor for myelosuppression and adjust doses accordingly 3, 5
• For gemcitabine, hold treatment if neutrophil count is less than 75,000/mm³ 3
• For paclitaxel, dose reductions are recommended for patients with severe neutropenia or peripheral neuropathy 5
• Patients should be monitored closely for immune-related adverse events when receiving checkpoint inhibitors 1

Metastatic TNBC remains a challenging disease with poor prognosis, but recent advances in immunotherapy, PARP inhibitors, and antibody-drug conjugates have expanded treatment options and improved outcomes for specific patient subgroups.