Pembrolizumab Treatment Protocol in Cancer Patients

Indications by Cancer Type

• The National Comprehensive Cancer Network recommends pembrolizumab as first-line treatment for metastatic Non-Small Cell Lung Cancer (NSCLC) with high PD-L1 expression (Tumor Proportion Score ≥50%) and no EGFR or ALK genomic aberrations 1, 2, 3
• The National Comprehensive Cancer Network recommends pembrolizumab as subsequent therapy for patients with metastatic nonsquamous or squamous NSCLC and PD-L1 expression who have progressed after platinum-based chemotherapy 1, 2, 3
• For patients with progression after first-line immunotherapy with pembrolizumab, the National Comprehensive Cancer Network recommends platinum-based chemotherapy as a second-line treatment option 2, 3
• The National Comprehensive Cancer Network recommends pembrolizumab as first-line therapy in patients with unresectable or metastatic melanoma 4, 5
• Pembrolizumab demonstrated improved response rate, progression-free survival, and overall survival compared with ipilimumab in patients with one or fewer prior systemic therapies, according to the National Comprehensive Cancer Network 4, 5
• The National Comprehensive Cancer Network recommends pembrolizumab as first-line therapy for patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer 6, 7
• The Journal of Clinical Oncology states that pembrolizumab is not recommended for patients with metastatic colorectal cancer and high tumor mutational burden (≥10 mutations/megabase) who have proficient mismatch repair 6, 7

Biomarker Testing

• The National Comprehensive Cancer Network recommends PD-L1 testing at diagnosis to inform the use of pembrolizumab in the first-line or second-line setting 2, 3
• The Journal of Clinical Oncology recommends determining microsatellite instability (MSI) or mismatch repair (MMR) status before initiating therapy for colorectal cancer patients 6, 7

Dosing and Administration

• The Annals of Oncology states that treatment may be prolonged if disease is controlled and toxicity is acceptable 2, 3

Safety Profile and Monitoring

• The National Comprehensive Cancer Network reports that grade 3-5 treatment-related adverse events occur in approximately 13-16% of patients 1
• Pembrolizumab is generally well-tolerated with fewer grade 3-5 treatment-related adverse events compared to chemotherapy (13% vs 35%), according to the National Comprehensive Cancer Network 1

Response Assessment

• The National Comprehensive Cancer Network states that median time to response is approximately 3 months (coinciding with first assessment at 12 weeks) 4, 5
• Late responses can be observed more than a year after starting treatment, according to the National Comprehensive Cancer Network 4, 5
• Initial partial responses may become complete responses with time, as reported by the National Comprehensive Cancer Network 4, 5
• Complete responses are highly durable, with 88% persisting after a median follow-up of 30 months, according to the National Comprehensive Cancer Network 4, 5

Special Populations

• The Annals of Oncology reports that elderly patients (>65 years) show equivalent efficacy and no difference in toxicity compared to younger patients 2, 3
• Immunotherapy should be considered for the treatment of elderly patients with metastatic NSCLC, according to the Annals of Oncology 2, 3

Common Pitfalls and Caveats

• Higher PD-L1 expression is generally associated with better response to pembrolizumab, but unselected patients may still benefit compared to chemotherapy, as stated by the Annals of Oncology 2, 3
• Progressive disease may be observed initially before response (pseudoprogression), requiring careful clinical assessment before discontinuing therapy, according to the National Comprehensive Cancer Network 4, 5
• In some patients with MSI-H or dMMR colorectal cancer, initial progressive disease may occur in 29% of cases despite overall survival benefit, as reported by the Journal of Clinical Oncology 6, 7

Pembrolizumab in Stage III MSI-High Colon Cancer

Current Regulatory Status and Evidence Base

• The FDA approved pembrolizumab in 2017 for unresectable or metastatic MSI-H/dMMR solid tumors that have progressed following prior treatment, based on a study of 149 patients with MSI-H/dMMR cancers across five multicenter trials, achieving an ORR of 39.6% with durable responses lasting ≥6 months in 78% of responders 8, 9, 10, 11
• The American Society of Clinical Oncology recommends first-line pembrolizumab for metastatic MSI-H/dMMR colorectal cancer, based on the KEYNOTE-177 trial, which demonstrated superior PFS (16.5 vs 8.2 months; HR 0.60) and improved OS (77.5 vs 36.7 months; HR 0.73) compared to chemotherapy 12

Efficacy and Safety

• Pembrolizumab monotherapy 200 mg IV every 3 weeks is preferred over chemotherapy for MSI-H/dMMR metastatic colorectal cancer, with an expected PFS of 16.5 months and significantly fewer grade 3-5 adverse events (22% vs 66% with chemotherapy) 12
• Grade 3-5 treatment-related adverse events occur in only 22% of patients receiving pembrolizumab, compared to 66-67% with chemotherapy 12