Keytruda (Pembrolizumab) Use in Lung Cancer Based on Disease Stage
Keytruda is primarily used in stage IV (metastatic) non-small cell lung cancer (NSCLC), with recent approvals for earlier stages including adjuvant therapy for resected stage IB-IIIA disease and neoadjuvant therapy for early-stage disease. 1, 2
Stage IV NSCLC Treatment Recommendations
Treatment recommendations are based on PD-L1 expression levels:
For PD-L1 Expression ≥50%:
- Pembrolizumab monotherapy is the preferred first-line treatment for patients with high PD-L1 expression (≥50%) without driver mutations 1
- Provides significant survival benefit with median overall survival of 30 months compared to 14 months with chemotherapy alone 1
- 5-year survival rates are significantly higher with pembrolizumab compared to chemotherapy 1
For PD-L1 Expression 1-49%:
- Combination therapy with pembrolizumab plus platinum-based chemotherapy is recommended 1
- In KEYNOTE-189 trial, this combination showed 5-year OS rates of 20.6% versus 7.6% for chemotherapy alone 1
- Alternative options include nivolumab plus ipilimumab or nivolumab/ipilimumab plus two cycles of platinum-based chemotherapy 1
For PD-L1 Expression <1% or Unknown:
- Pembrolizumab plus platinum-based chemotherapy is recommended 1
- For non-squamous NSCLC: pembrolizumab with platinum and pemetrexed 1
- For squamous NSCLC: pembrolizumab with carboplatin and paclitaxel/nab-paclitaxel 1
- Alternative options include nivolumab plus ipilimumab or nivolumab/ipilimumab plus chemotherapy 1
Earlier Stage NSCLC Applications
Adjuvant Therapy:
- FDA-approved for adjuvant treatment after resection and platinum-based chemotherapy for stage IB (≥4 cm), II, or IIIA NSCLC 2, 3
- PEARLS/KEYNOTE-091 trial showed significant improvement in disease-free survival (53.6 months vs 42.0 months) compared to placebo 3
Neoadjuvant Therapy:
- Approved in combination with platinum-based chemotherapy before surgery for resectable early-stage NSCLC 2
- Continued as single-agent after surgery to prevent recurrence 2
Important Considerations
- PD-L1 testing is crucial for treatment selection in stage IV disease 1
- Higher PD-L1 expression correlates with better outcomes with pembrolizumab treatment 4, 5
- Contraindications include severe autoimmune diseases, organ transplantation, or other conditions that preclude immunotherapy 1
- Common immune-related adverse events include thyroid dysfunction, hepatitis, and pneumonitis 6
Treatment Sequencing
- For patients who progress on pembrolizumab monotherapy: platinum-doublet chemotherapy is recommended 1
- For patients who progress on pembrolizumab plus chemotherapy: docetaxel with or without ramucirumab is recommended 1
Keytruda has revolutionized lung cancer treatment across multiple stages, with the most established benefit in stage IV disease, but expanding applications in earlier stages with curative intent.