Pembrolizumab Indications and Efficacy

Current Indications for Pembrolizumab

The National Comprehensive Cancer Network (NCCN) recommends pembrolizumab as a category 2A treatment option for recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) that has progressed on or after platinum-based chemotherapy 1
The FDA approved pembrolizumab for first-line treatment of metastatic Non-Small Cell Lung Cancer (NSCLC) with high PD-L1 expression (Tumor Proportion Score ≥50%) with no EGFR or ALK genomic aberrations 3
The NCCN recommends pembrolizumab as a first-line treatment for patients with locally advanced or metastatic urothelial carcinoma that has progressed during or after platinum-based chemotherapy, or as a first-line treatment for patients who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (combined positive score ≥10) 4, 5
The NCCN recommends pembrolizumab for mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer, with a category 1 recommendation for second-line therapy based on phase III trial showing longer median overall survival compared to chemotherapy (10.3 vs 7.4 months, p=0.002) 6, 7, 8

PD-L1 expression is an important biomarker for response in multiple tumor types, with higher response rates observed in PD-L1 positive tumors (≥1% expression) compared to PD-L1 negative tumors (22% vs 4%, p=0.021) 1, 2, 4
Microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) is predictive of response across tumor types, with immune-related objective response rates of 40% in dMMR colorectal cancer compared to 0% in MMR-proficient colorectal cancer 2, 6, 7
Tumor mutational burden (TMB) is associated with better response to pembrolizumab, with higher response rates in TMB-high tumors compared to non-TMB high tumors (29% vs 6%) 2

Pembrolizumab is generally well-tolerated with grade 3/4 toxicities reported in 9-16% of patients across studies, and common immune-related adverse events include pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions 1, 4, 5

Pembrolizumab may be offered to patients with tumor mutational burden (TMB)-high recurrent or metastatic rare head and neck cancers, or recurrent or metastatic salivary gland cancers with PD-L1 expression ≥1% 2
The American Society of Clinical Oncology (ASCO) and NCCN recommend proper testing for PD-L1, MSI/MMR status, or TMB before initiating pembrolizumab therapy, as response to pembrolizumab may vary based on biomarker status 1, 2, 8