First-Line Treatment for Metastatic Triple-Negative Breast Cancer
For immunotherapy-eligible patients (PD-L1-positive), atezolizumab plus nab-paclitaxel or pembrolizumab plus chemotherapy is the standard first-line treatment, with atezolizumab plus nab-paclitaxel improving overall survival from 15.1 to 25 months (7-month benefit) in PD-L1-positive disease. 1
Treatment Algorithm Based on PD-L1 Status and BRCA Mutation
PD-L1-Positive Disease (First Priority)
Atezolizumab plus nab-paclitaxel is the preferred regimen, demonstrating progression-free survival improvement from 5.0 to 7.5 months (HR 0.62, P<0.001) and overall survival benefit of 25 versus 15.1 months in PD-L1-positive patients (≥1% immune cell staining using SP142 assay). 1, 2
Pembrolizumab plus chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin) is an alternative option, improving progression-free survival from 5.6 to 9.7 months (HR 0.65, P=0.0012) for patients with combined positive score ≥10 using the 22C3 assay. 1, 2
Critical caveat: Immunotherapy is only indicated if metastatic disease developed de novo or at least 12 months after completion of (neo)adjuvant chemotherapy. 1, 2
PD-L1-Negative Disease (Second Priority)
Weekly paclitaxel is the preferred single-agent chemotherapy if not previously used in the adjuvant setting, as taxane-based regimens have level 1 evidence for first-line therapy. 1, 3
Carboplatin is an important alternative option, demonstrating comparable efficacy to docetaxel with a more favorable toxicity profile in triple-negative breast cancer patients previously treated with anthracyclines with or without taxanes. 1
The TNT trial showed similar overall response rates between carboplatin (31.4%) and docetaxel (34.0%) in first-line metastatic TNBC, but carboplatin had better tolerability. 3
BRCA Mutation Considerations
For patients with both PD-L1-positive disease and germline BRCA1/2 mutations, the selection between immunotherapy or PARP inhibitor for first-line treatment remains debated, though immunotherapy plus chemotherapy is generally prioritized in the first-line setting. 1
Carboplatin demonstrates particular efficacy in BRCA-mutated TNBC with increased objective response rates, but this does not translate to overall survival benefit compared to docetaxel. 1, 3
PARP inhibitors (olaparib or talazoparib) are reserved for later lines in BRCA-mutated patients who have received prior chemotherapy, not as first-line therapy. 1, 3
Key Treatment Principles
Sequential single-agent chemotherapy is preferred over combination regimens to minimize toxicity, except in cases of visceral crisis or rapidly progressing disease requiring immediate response. 1, 3
Combination chemotherapy should only be used for symptomatic visceral crisis, immediately life-threatening disease, or rapidly progressive disease with risk of patient deterioration—triple-negative biology alone does not mandate combination therapy. 3
Common Pitfalls to Avoid
Do not use different PD-L1 assays interchangeably: SP142 assay is required for atezolizumab (≥1% immune cell staining), while 22C3 assay is required for pembrolizumab (CPS ≥10). 2
Do not initiate immunotherapy if disease recurred within 12 months of completing (neo)adjuvant chemotherapy—this is an exclusion criterion for immunotherapy benefit. 1, 2
Do not reserve carboplatin only for BRCA-mutated patients: carboplatin is an appropriate option for all triple-negative breast cancer patients regardless of BRCA status, particularly after prior anthracycline exposure. 1
Checkpoint inhibitor monotherapy in later lines is not recommended due to low response rates (KEYNOTE-199 trial), so immunotherapy must be combined with chemotherapy in first-line setting. 1