Pembrolizumab

• Non-Small Cell Lung Cancer
• Melanoma
• Head and Neck Cancer
• Hodgkin Lymphoma
• MSI-H Cancers

Pembrolizumab is a humanized monoclonal antibody that targets programmed cell death protein 1 (PD-1), making it one of the most widely used immune checkpoint inhibitors in oncology. It has revolutionized cancer treatment across numerous tumor types by unleashing the immune system to fight cancer.

Mechanism of Action

Pembrolizumab works by blocking the PD-1 immune checkpoint:

• PD-1 receptor blockade: Binds to PD-1 on T cells, preventing interaction with its ligands PD-L1 and PD-L2
• Restores T cell function: Removes the "brake" that tumors use to evade immune destruction
• Enhances antitumor immunity: Reactivated T cells can recognize and kill cancer cells
• Immunological memory: May provide durable responses even after treatment completion

Tumors often exploit the PD-1/PD-L1 pathway to escape immune surveillance; pembrolizumab disrupts this mechanism.

Available Formulations

Pembrolizumab is available as:

• IV solution: 25 mg/mL in 4 mL single-dose vial (100 mg)
• IV injection: 100 mg/4 mL, 25 mg/mL

Administered as IV infusion over 30 minutes.

Medical Uses

FDA-Approved Indications (Selected):

• Non-small cell lung cancer (multiple settings)
• Head and neck squamous cell carcinoma
• Classical Hodgkin lymphoma
• Primary mediastinal B-cell lymphoma
• Melanoma (adjuvant and metastatic)
• Urothelial carcinoma
• Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) cancers
• Gastric/GEJ adenocarcinoma
• Cervical cancer
• Hepatocellular carcinoma
• Merkel cell carcinoma
• Renal cell carcinoma
• Endometrial carcinoma
• Triple-negative breast cancer
• Many others (see full prescribing information)

Dosing Guidelines

Standard Dosing:

• 200 mg IV every 3 weeks, or
• 400 mg IV every 6 weeks

Duration:

• Until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression
• Some adjuvant settings have defined treatment durations (e.g., 12 months for melanoma)

Dose Modifications:

• No dose reductions; withhold or permanently discontinue for immune-related adverse events

Important Safety Information

Immune-Mediated Adverse Reactions (Can Be Fatal):

• Pneumonitis: Monitor for respiratory symptoms
• Colitis: Monitor for diarrhea and abdominal pain
• Hepatitis: Monitor liver function before and during treatment
• Endocrinopathies: Thyroiditis, hypophysitis, adrenal insufficiency, type 1 diabetes
• Nephritis: Monitor renal function
• Dermatologic reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis
• Myocarditis: Monitor for cardiac symptoms

Management:

• Withhold for moderate immune-related reactions
• Corticosteroids for most immune-related adverse events
• Permanently discontinue for severe or life-threatening reactions

Drug Interactions

No formal drug interaction studies conducted. As an antibody, pembrolizumab is not expected to interact via cytochrome P450 pathways.

• Systemic corticosteroids: Avoid before starting; may be used for immune-related adverse events
• Other immunosuppressants: May reduce efficacy

Special Populations

• Hepatic Impairment: No adjustment for mild; limited data for moderate/severe
• Renal Impairment: No adjustment needed
• Pregnancy: Can cause fetal harm; verify pregnancy status before starting
• Lactation: Discontinue breastfeeding during treatment
• Autoimmune diseases: Use with caution; may exacerbate underlying conditions