Is Keytruda (pembrolizumab) safe to use?

Safety Profile of Keytruda (Pembrolizumab)

Keytruda (pembrolizumab) is generally safe with manageable side effects, but requires monitoring for immune-related adverse events that can affect multiple organ systems. 1

Safety Profile Overview

Pembrolizumab has demonstrated a favorable safety profile compared to traditional chemotherapy, with fewer grade 3-5 treatment-related adverse events. In clinical trials for non-small cell lung cancer (NSCLC), pembrolizumab showed significantly lower rates of severe adverse events (13-16%) compared to docetaxel (35%) 2.

Common Side Effects

• Fatigue
• Pruritus (itching)
• Diarrhea
• Anorexia (decreased appetite)
• Constipation
• Nausea
• Rash
• Fever
• Cough
• Dyspnea (shortness of breath)
• Musculoskeletal pain 2, 1

Immune-Mediated Adverse Events

Pembrolizumab can trigger immune-related adverse events that require special attention:

• Colitis
• Hepatitis
• Endocrinopathies (thyroid dysfunction, most common)
• Pneumonitis
• Nephritis 2, 1

Safety in Special Populations

Elderly Patients

• No overall differences in safety or effectiveness between elderly and younger patients in most cancer types
• Higher incidence of serious adverse reactions (50%) in patients ≥65 years with classical Hodgkin lymphoma compared to younger patients (24%) 1

Pediatric Patients

Safety established in pediatric patients with melanoma, classical Hodgkin lymphoma, and other specific indications. Adverse reactions occurring at higher rates in pediatric patients compared to adults include:

• Pyrexia (33%)
• Vomiting (29%)
• Headache (25%)
• Abdominal pain (23%)
• Decreased lymphocyte count (13%)
• Decreased white blood cell count (11%) 1

Patients with HIV

In a phase 1 study of patients with HIV and advanced cancer:

• Most treatment-emergent adverse events were grade 1-2
• Only 20% experienced grade 3 events
• HIV remained well-controlled in all participants
• Pembrolizumab showed acceptable safety in patients with CD4+ T-cell counts >100 cells/μL 3

Contraindications and Precautions

Pregnancy and Breastfeeding

• Can cause fetal harm based on mechanism of action
• Women should use effective contraception during treatment and for 4 months after the last dose
• Not recommended during breastfeeding 1

Pre-existing Conditions

Special caution in patients with:

• Immune system disorders (e.g., Crohn's disease, ulcerative colitis, lupus)
• History of organ or tissue transplant
• Previous or planned stem cell transplant
• Neurological conditions (myasthenia gravis, Guillain-Barré syndrome) 1

Monitoring Recommendations

1. Baseline Assessment: Complete blood count, liver function tests, thyroid function tests, and kidney function tests before initiating therapy

2. Regular Monitoring:

   • Blood tests to check for immune-related adverse events
   • Thyroid function tests (hypothyroidism is common)
   • Liver function tests
   • Assessment for new or worsening respiratory symptoms

3. Patient Education: Instruct patients to report symptoms such as:

   • Persistent diarrhea
   • Severe abdominal pain
   • Shortness of breath
   • Unusual fatigue
   • Skin rash
   • Changes in urine or stool color

Efficacy Considerations

While safety is the primary concern, it's worth noting that pembrolizumab has shown significant efficacy across multiple tumor types:

• In NSCLC, improved overall survival compared to chemotherapy 2
• Durable responses in MSI-H or dMMR tumors across multiple cancer types 2
• Effective in patients with high PD-L1 expression 2

Conclusion

Keytruda (pembrolizumab) has a manageable safety profile with most adverse events being mild to moderate in severity. The risk of immune-related adverse events requires vigilant monitoring but is generally manageable with appropriate intervention. The benefit-risk profile is favorable for approved indications, with significantly fewer severe adverse events compared to traditional chemotherapy.