What are the recommended immunotherapy options for patients with metastatic lung cancer?

Immunotherapy Options for Metastatic Lung Cancer

PD-1/PD-L1 inhibitors are the cornerstone of immunotherapy treatment for metastatic non-small cell lung cancer (NSCLC), with specific regimens determined by PD-L1 expression levels, histology, and patient characteristics. 1

First-Line Treatment Algorithm Based on PD-L1 Expression

High PD-L1 Expression (≥50%)

• Pembrolizumab monotherapy is the preferred first-line treatment 1, 2
  • Offers superior survival benefit (median OS 30 months vs 14 months with chemotherapy)
  • Associated with improved quality of life and fewer adverse events
  • ESMO-MCBS v1.1 score: 5 (highest clinical benefit)

Any PD-L1 Expression Level

• Combination immunotherapy-chemotherapy options:
  • For non-squamous histology: Pembrolizumab + pemetrexed + platinum 1
  • For squamous histology: Pembrolizumab + carboplatin + (nab)-paclitaxel 1, 3
  • Alternative combinations:
    • Atezolizumab + bevacizumab + carboplatin + paclitaxel (non-squamous only) 1, 4
    • Atezolizumab + carboplatin + nab-paclitaxel (non-squamous only) 1, 4
    • Nivolumab + ipilimumab + 2 cycles of platinum-doublet chemotherapy 1, 5

Second-Line Treatment Options

After First-Line Chemotherapy (PD-L1 Inhibitor-Naive)

• PD-1/PD-L1 inhibitors are treatment of choice 1:
  • Nivolumab (for both squamous and non-squamous NSCLC) 1, 5
  • Pembrolizumab (for patients with PD-L1 expression ≥1%) 1
  • Atezolizumab (after one or two prior lines of chemotherapy) 1, 4

After First-Line Immunotherapy

• Platinum-based chemotherapy is recommended for patients progressing after first-line pembrolizumab 1

Special Considerations

Patient Selection Factors

• PD-L1 testing is essential before initiating treatment 1, 2
• Better outcomes with immunotherapy are observed in:
  • Patients with history of smoking
  • Male gender
  • Age <65 years 2

Treatment Duration and Monitoring

• Treatment may be prolonged if disease is controlled and toxicity is acceptable 1
• Immunotherapy can be discontinued after 2 years of treatment in responding patients 2

Performance Status Considerations

• For PS 0-1: Standard immunotherapy options as above
• For PS 2: Consider carboplatin-based doublets or monotherapy immunotherapy in selected cases 1, 2
• For PS 3-4: Best supportive care is recommended 1, 2

Pitfalls and Caveats

1. Contraindications to immunotherapy:

   • Severe autoimmune disease
   • Organ transplantation
   • Untreated brain metastases (relative contraindication)

2. Histology-specific considerations:

   • Pemetrexed is restricted to non-squamous histology
   • Bevacizumab is contraindicated in squamous NSCLC due to risk of pulmonary hemorrhage

3. Malignant pleural effusion may predict poorer response to pembrolizumab monotherapy, even with high PD-L1 expression 6

4. Real-world data suggests combination therapy may provide superior early survival benefits over monotherapy in PD-L1-high patients, particularly in females, stage IVB disease, and PD-L1 expression >75% 7

5. Pseudo-progression can occur with immunotherapy, requiring careful evaluation before changing treatment

By following this evidence-based algorithm, clinicians can optimize immunotherapy selection for patients with metastatic lung cancer to improve survival outcomes and quality of life.