Is Pembrolizumab a recognized medication?

Pembrolizumab (Keytruda) is an FDA-approved PD-1 inhibitor immunotherapy medication used to treat multiple cancer types, demonstrating significant survival benefits across various malignancies.

Pembrolizumab is a well-established, FDA-approved monoclonal antibody that targets the PD-1 receptor, used for treating multiple cancer types including melanoma, non-small cell lung cancer, head and neck cancer, bladder cancer, and gastric cancer.

Mechanism of Action and Efficacy

Pembrolizumab works by blocking the interaction between PD-1 and its ligands (PD-L1 and PD-L2), which:

• Releases PD-1-mediated inhibition of the immune response
• Enhances antitumor immunity by allowing T-cells to recognize and attack cancer cells 1
• Is particularly effective in tumors with high mutation burdens 2

FDA-Approved Indications

Pembrolizumab has received FDA approval for multiple cancer types:

1. Melanoma:

   • First-line therapy for patients with PD-L1 expression levels ≥50% (category 1) 2
   • Adjuvant therapy for up to 52 weeks 2

2. Non-Small Cell Lung Cancer (NSCLC):

   • First-line therapy for patients with PD-L1 expression ≥50% and negative for EGFR mutations, ALK and ROS1 rearrangements (category 1) 2
   • Subsequent therapy for metastatic NSCLC (category 1) 2

3. Head and Neck Squamous Cell Carcinoma:

   • Treatment for recurrent or metastatic disease that has progressed on or after platinum-based chemotherapy (category 2A) 2

4. Bladder Cancer (Urothelial Carcinoma):

   • First-line treatment for locally advanced or metastatic disease in cisplatin-ineligible patients with PD-L1 expression 2
   • Second-line therapy after platinum-based chemotherapy (category 1) 2

5. Gastric and Gastroesophageal Junction Cancer:

   • First-line therapy in combination with trastuzumab and chemotherapy for HER2-positive tumors with PD-L1 CPS ≥1 (category 1) 2
   • First-line therapy with chemotherapy for HER2-negative tumors with PD-L1 CPS ≥1 (category 1 when CPS ≥5) 2

6. MSI-H/dMMR Tumors:

   • Treatment for unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment 2, 3

Dosing Regimens

Common dosing regimens include:

• 200 mg IV every 3 weeks 2
• 400 mg IV every 6 weeks (EU EMA-approved) 2
• 10 mg/kg IV every 2 or 3 weeks (in earlier trials) 2

Efficacy Data

Pembrolizumab has demonstrated significant clinical benefits:

• Melanoma: Superior to ipilimumab in stage III/IV unresectable disease 1
• NSCLC: Response rates of 19-25% in refractory disease 1
• Bladder Cancer: Longer median OS compared to chemotherapy (10.3 vs 7.4 months) with fewer grade 3-5 adverse events (15.0% vs 49.4%) 2
• MSI-H/dMMR Tumors: Overall response rate of 30.8% with durable responses (median duration of response 47.5 months) 3
• Gastric Cancer: Improved OS and PFS when combined with chemotherapy in HER2-negative disease with PD-L1 CPS ≥1 2

Predictive Biomarkers

Response to pembrolizumab is associated with:

• PD-L1 expression levels (higher expression generally correlates with better response) 2
• MSI-H/dMMR status (strong predictor of response across tumor types) 2, 3
• High tumor mutation burden 1

Adverse Events

Common adverse events include:

• Fatigue and rash (most common) 4
• Immune-related adverse events:
  • Thyroid dysfunction
  • Hepatitis
  • Pneumonitis
  • Nephritis 5, 6

Grade 3-4 toxicities occur in approximately 10-15% of patients 1, 3

Clinical Considerations

• PD-L1 testing is recommended before initiating treatment for certain indications
• Companion diagnostic tests have been FDA-approved for measuring PD-L1 expression 2
• Patients should be monitored for immune-related adverse events, which may require treatment discontinuation
• Response patterns may differ from conventional chemotherapy, with some patients experiencing pseudoprogression before response

Pembrolizumab represents a significant advancement in cancer immunotherapy with demonstrated survival benefits across multiple tumor types, particularly those with specific biomarkers like PD-L1 expression or MSI-H/dMMR status.