What do the American Society of Clinical Oncology (ASCO) guidelines recommend for the use of immunotherapy, specifically pembrolizumab (pembrolizumab), in triple-negative breast cancer?

ASCO Guidelines for Immunotherapy in Triple-Negative Breast Cancer

ASCO strongly recommends adding immune checkpoint inhibitors (pembrolizumab or atezolizumab) to chemotherapy as first-line therapy for patients with metastatic PD-L1-positive triple-negative breast cancer. 1

PD-L1 Testing Requirements

• PD-L1 positivity determination is essential before initiating immunotherapy
  • For pembrolizumab: Use 22C3 companion assay with CPS ≥10 considered positive 1
  • For atezolizumab: Use Ventana SP142 antibody with immune cell score ≥1% considered positive 1
• Different assays yield different results - must use the specific assay validated for each immunotherapy agent 1

First-Line Treatment Algorithm

1. For PD-L1-positive metastatic TNBC (CPS ≥10):

   • Pembrolizumab plus chemotherapy is the preferred option
   • Provides significant survival benefit: 23.0 months vs 16.1 months with chemotherapy alone (HR 0.73) 2
   • Chemotherapy options include nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin

2. For PD-L1-negative metastatic TNBC:

   • Single-agent chemotherapy is preferred over combination chemotherapy 1
   • Exception: Combination regimens may be considered for symptomatic or immediately life-threatening disease 1

3. Important pairing considerations:

   • Atezolizumab should specifically be paired with nab-paclitaxel, not paclitaxel 1
   • IMpassion131 trial showed no PFS improvement when atezolizumab was paired with paclitaxel 1

Efficacy Data

• Pembrolizumab + chemotherapy (KEYNOTE-355 trial):

  • In PD-L1 CPS ≥10 patients: Median OS 23.0 vs 16.1 months (HR 0.73) 2
  • PFS improvement: 9.7 vs 5.6 months (HR 0.65) 1

• Atezolizumab + nab-paclitaxel (IMpassion130 trial):

  • In PD-L1-positive subset: OS 25 vs 15.5 months (HR 0.62) 1
  • PFS improvement: 7.5 vs 5 months (HR 0.62) 1

Safety Considerations

• Common adverse events with immunotherapy:

  • Thyroid dysfunction: 23% with atezolizumab 1
  • Other immune-related adverse events: ~10% 1
  • Grade 3-4 events: Similar between pembrolizumab-chemotherapy (68%) and chemotherapy alone (67%) 1, 2

• Treatment-related deaths:

  • Atezolizumab: 0.7% (3/451 patients) 1
  • Pembrolizumab: 0.4% in combination therapy 2

• Special considerations:

  • Caution in patients with history of autoimmune disease 1
  • Monitor for immune-mediated adverse events, particularly thyroid dysfunction 1
  • Treatment discontinuation rates: 16% with atezolizumab vs 8% with placebo 1

Additional Testing Recommendations

• dMMR/MSI-H testing:
  • Recommended for all metastatic TNBC patients who are candidates for immunotherapy 1
  • Positive results may indicate eligibility for dostarlimab-gxly or pembrolizumab monotherapy 1

Early-Stage TNBC Considerations

• Neoadjuvant pembrolizumab plus chemotherapy has shown promising results:
  • Significantly improved pathological complete response rates 3
  • Improved event-free survival: 84.5% vs 76.8% at 36 months (HR 0.63) 3

Clinical Pearls

• PD-L1 testing is complex and assay-specific - using the wrong test may lead to inappropriate treatment selection 1
• Immunotherapy should be initiated as first-line therapy in eligible patients to maximize survival benefit 1
• Regular monitoring for immune-related adverse events is essential, with prompt management when detected 1
• The survival benefit of immunotherapy is most pronounced in patients with higher PD-L1 expression 2