What is the recommended treatment protocol for Pembrolizumab (pembrolizumab) in cancer patients?

Pembrolizumab Treatment Protocol in Cancer Patients

Pembrolizumab is recommended at a standard dose of 200 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in cancer patients, with specific indications based on cancer type and biomarker status. 1, 2

Indications by Cancer Type

Non-Small Cell Lung Cancer (NSCLC)

• First-line treatment for metastatic NSCLC with high PD-L1 expression (Tumor Proportion Score ≥50%) with no EGFR or ALK genomic aberrations 3
• Subsequent therapy for patients with metastatic nonsquamous or squamous NSCLC and PD-L1 expression who have progressed after platinum-based chemotherapy 3
• For patients with progression after first-line immunotherapy with pembrolizumab, platinum-based chemotherapy is recommended as a second-line treatment option 3
• Five-year overall survival rate with pembrolizumab as first-line therapy for metastatic NSCLC with PD-L1 ≥50% is 31.9% compared to 16.3% with chemotherapy 4

Melanoma

• First-line therapy in patients with unresectable or metastatic melanoma 3, 5
• Pembrolizumab demonstrated improved response rate, progression-free survival, and overall survival compared with ipilimumab in patients with one or fewer prior systemic therapies 3
• Responses to pembrolizumab are very long-lived, with median duration ranging from 23 months to much longer (not reached even after 33.9 months follow-up) 3

Colorectal Cancer

• First-line therapy for patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer 3
• Not recommended for patients with metastatic colorectal cancer and high tumor mutational burden (≥10 mutations/megabase) who have proficient mismatch repair 3

Other Indications

• Treatment for recurrent or metastatic head and neck squamous cell carcinoma that has progressed on or after platinum-based chemotherapy 6, 1
• Treatment for locally advanced or metastatic urothelial carcinoma that has progressed during or after platinum-based chemotherapy 6
• Treatment for patients with unresectable or metastatic, microsatellite instability-high or mismatch repair deficient solid tumors that have progressed after prior treatment 3, 6

Biomarker Testing

• PD-L1 testing is routinely recommended at diagnosis to inform the use of pembrolizumab in the first-line or second-line setting 3, 6
• Microsatellite instability (MSI) or mismatch repair (MMR) status should be determined before initiating therapy for colorectal cancer patients 3, 6
• Tumor mutational burden (TMB) testing may be considered for certain tumor types, with higher response rates observed in TMB-high tumors 6

Dosing and Administration

• Standard dose: 200 mg intravenously every 3 weeks 1, 2
• Treatment should continue until disease progression, unacceptable toxicity, or up to 24 months 1, 2
• Treatment may be prolonged if disease is controlled and toxicity is acceptable 3
• For patients who achieve complete response, treatment may be discontinued after 24 months 1

Safety Profile and Monitoring

• Grade 3-5 treatment-related adverse events occur in approximately 13-16% of patients 3, 2
• Common immune-related adverse events include pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions 6, 2, 5
• Patients should be monitored for immune-mediated adverse reactions during and after treatment 1
• Pembrolizumab is generally well-tolerated with fewer grade 3-5 treatment-related adverse events compared to chemotherapy (13% vs 35%) 3

Response Assessment

• Median time to response is approximately 3 months (coinciding with first assessment at 12 weeks) 3
• Late responses can be observed more than a year after starting treatment 3
• Initial partial responses may become complete responses with time 3
• Complete responses are highly durable, with 88% persisting after a median follow-up of 30 months 3

Special Populations

• Elderly patients (>65 years) show equivalent efficacy and no difference in toxicity compared to younger patients 3
• Immunotherapy should be considered for the treatment of elderly patients with metastatic NSCLC 3
• For patients not suitable for immunotherapy, second-line chemotherapy is recommended 3

Common Pitfalls and Caveats

• Pembrolizumab is not recommended for patients with active autoimmune disease requiring systemic therapy or medical conditions requiring immunosuppression 1
• Higher PD-L1 expression is generally associated with better response to pembrolizumab, but unselected patients may still benefit compared to chemotherapy 3
• Progressive disease may be observed initially before response (pseudoprogression), requiring careful clinical assessment before discontinuing therapy 3
• In some patients with MSI-H or dMMR colorectal cancer, initial progressive disease may occur in 29% of cases despite overall survival benefit 3