What are the treatment options for advanced non-small cell lung cancer (NSCLC) using immunotherapy, such as pembrolizumab (pembrolizumab) or nivolumab (nivolumab)?

Immunotherapy Options for Advanced Non-Small Cell Lung Cancer

Pembrolizumab, either as monotherapy for patients with high PD-L1 expression (≥50%) or in combination with platinum-based chemotherapy regardless of PD-L1 status, is the standard first-line treatment for patients with advanced NSCLC without targetable mutations. 1

First-Line Treatment Options Based on PD-L1 Expression

For PD-L1 Expression ≥50%:

• Pembrolizumab monotherapy is the preferred option with significant survival benefit (median OS 30 months vs 14 months with chemotherapy) 1

  • Particularly effective in squamous NSCLC subgroup (HR = 0.35) 1
  • Associated with improved quality of life and fewer adverse events than chemotherapy 1
  • ESMO-MCBS v1.1 score: 5 (highest clinical benefit) 1

• Alternative options:

  • Atezolizumab monotherapy 1
  • Cemiplimab monotherapy 1
  • Pembrolizumab + chemotherapy (if rapid tumor reduction needed) 1

For PD-L1 Expression <50% or Regardless of PD-L1 Status:

• Pembrolizumab + platinum-based chemotherapy is recommended 1

  • For non-squamous histology: pembrolizumab + pemetrexed + platinum 1
  • For squamous histology: pembrolizumab + carboplatin + (nab)-paclitaxel 1
  • Significant improvement in overall survival regardless of PD-L1 expression 2

• Alternative combination options:

  • Nivolumab + ipilimumab + two cycles of chemotherapy 1
  • Atezolizumab + bevacizumab + paclitaxel + carboplatin (non-squamous only) 1
  • Atezolizumab + carboplatin + nab-paclitaxel (non-squamous only) 1

Treatment Duration and Special Populations

• Duration: Immunotherapy can be discontinued after 2 years of treatment 1
• Performance Status (PS) 2: Consider platinum-based doublets (preferably carboplatin) or monotherapy ICI in selected cases 1
• Elderly patients: Similar recommendations as general population, but benefit of chemo-immunotherapy combinations less clear in patients ≥75 years 1, 3
• PS 3-4: Best supportive care recommended 1

Second-Line Treatment Options

After progression on first-line immunotherapy:

• If prior benefit from immunotherapy: Consider rechallenge with immunotherapy 1
• If no prior immunotherapy: Nivolumab, pembrolizumab (if PD-L1 ≥1%), or atezolizumab 1

Predictive Factors for Immunotherapy Response

Several clinical factors may predict benefit from pembrolizumab-based therapy:

• Better outcomes in patients:
  • Age <65 years
  • Male gender
  • History of smoking
  • PD-L1 TPS ≥50% or <1% (with combination therapy)
• Less benefit observed in:
  • Age ≥75 years
  • Female gender
  • Never-smokers
  • PD-L1 TPS 1-49% 3

Important Considerations and Caveats

• PD-L1 testing: Essential before initiating treatment to determine optimal therapy
• Contraindications to immunotherapy: Severe autoimmune disease, organ transplantation
• Histology-specific considerations:
  • Pemetrexed is restricted to non-squamous histology 1
  • Bevacizumab is contraindicated in squamous NSCLC due to risk of pulmonary hemorrhage 1
• Immune-related adverse events: Monitor for pneumonitis, thyroid dysfunction, colitis, hepatitis, and other immune-mediated toxicities

Immunotherapy has revolutionized the treatment of advanced NSCLC, significantly improving survival outcomes compared to traditional chemotherapy alone. The choice between monotherapy and combination approaches should be guided by PD-L1 expression levels, histology, and the need for rapid disease control.