PD-L1 Testing for Pembrolizumab in Stage 4 Gastric Adenocarcinoma

Introduction to PD-L1 Testing

The National Comprehensive Cancer Network recommends PD-L1 testing to guide optimal treatment selection and maximize survival benefit in stage 4 gastric adenocarcinoma 1, 2

For HER2-negative gastric/GEJ adenocarcinoma, the National Comprehensive Cancer Network recommends PD-L1 testing using an FDA-approved companion diagnostic test (22C3 pharmDx) in a CLIA-approved laboratory 1, 2
The strongest evidence (Category 1 recommendation) exists for patients with PD-L1 CPS ≥5, where pembrolizumab plus chemotherapy demonstrated superior overall survival 3
For patients with CPS ≥1, pembrolizumab plus chemotherapy showed median OS of 13 months versus 11.4 months with chemotherapy alone (HR 0.74, P <0.0001) 3
For patients with CPS ≥10, the survival benefit is most pronounced with median OS of 15.7 months versus 11.8 months (HR 0.65, P <0.0001) 3

PD-L1 testing is NOT required for MSI-H or dMMR gastric cancers, as pembrolizumab monotherapy is approved regardless of PD-L1 status for these tumors 3, 4, 5
Universal MSI/MMR testing should be performed for all newly diagnosed gastric cancers, as MSI-H tumors showed 31% objective response rate to pembrolizumab in KEYNOTE-158 3, 4

A minimum of 100 viable tumor cells must be present in the PD-L1-stained slide for adequate evaluation, and testing should be performed on formalin-fixed paraffin-embedded (FFPE) tissue 1, 2, 4
The Combined Positive Score (CPS) is calculated as: (number of PD-L1-staining cells [tumor cells, lymphocytes, macrophages] / total viable tumor cells) × 100, and a specimen is considered PD-L1-positive if CPS ≥1 1, 2, 4

The National Comprehensive Cancer Network recommends performing universal MSI/MMR testing first, followed by HER2 testing, and then PD-L1 testing using an FDA-approved companion diagnostic 1, 2, 3, 4, 5
Treatment selection should be based on biomarkers, with HER2-positive + PD-L1 CPS ≥1 patients receiving pembrolizumab + trastuzumab + chemotherapy, and HER2-negative + PD-L1 CPS ≥5 patients receiving pembrolizumab + chemotherapy 3